You searched for subject:(DNA structure)
.
Showing records 1 – 30 of
301 total matches.
◁ [1] [2] [3] [4] [5] … [11] ▶

University of Cambridge
1.
LI, ZHE.
Effect of Naturally Occurring DNA Modifications on DNA Structure and Packaging.
Degree: PhD, 2019, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/289658
► In eukaryotes, the genomic double-stranded DNA (dsDNA) coils around histones to form nucleosomes. Arrays of these nucleosomes bundle together to generate chromatin. Most DNA-related processes…
(more)
▼ In eukaryotes, the genomic double-stranded DNA (dsDNA) coils around histones to form nucleosomes. Arrays of these nucleosomes bundle together to generate chromatin. Most DNA-related processes require interactions between chromatin-protected DNA and cellular machinery. Access of cell machinery to genomic DNA is partially regulated by the position and stability of nucleosomes, which may be influenced by changes in nucleosomal DNA. DNA is composed of adenine (A), guanine (G), cytosine (C), thymine (T) nucleotides and their derivatives. It has been shown that some C derivatives participate in directing multiple biological processes, and aberrant modification patterns are often linked to diseases. It has been proposed that T derivatives exhibit similar effects. This thesis focuses on elucidating the effect of naturally occurring DNA modifications on the properties of dsDNA and nucleosomes.
dsDNA sequences systematically modified with various T derivatives were characterized using classical biophysical techniques to assess the effect of these DNA modifications. The results indicate that in the sequence context studied, 5-hydroxymethyluracil modifications destabilize dsDNA, while dense symmetrical 5-formyluracil (fU) modifications alter the dsDNA structure. These effects may provide clues to the differential protein recruitment observed in previous research.
In vitro studies on nucleosome occupancy and stability revealed that 5-formylcytosine (fC) modifications have positive effects on nucleosome formation and stability compared to the unmodified counterpart by influencing the intrinsic biochemical and biophysical properties of the nucleosomes. These results provide casual links for the observation in vivo between fC and the increased nucleosome occupancy and positioning. In order to further understand the positional effect of fC on the nucleosomes, a method was developed for quick and reliable incorporation of C derivatives into dsDNA at desired positions.
The positive effect of fC modifications on nucleosome occupancy and stability observed here has necessitated further studies to gain deeper insights into the biological functions of fC in the nucleosome context. Cryo-EM can be used to elucidate the structural foundation for the changes fC posts to nucleosome, and protein interacting assays will identify the cellular machineries specifically recruited/repulsed by fC-modified nucleosomes.
The effect of DNA modifications elucidated by the above studies advances our understanding on the role that DNA modifications play in regulating cellular processes.
Subjects/Keywords: nucleosome; DNA Modifications; DNA Structure; DNA Packaging
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
LI, Z. (2019). Effect of Naturally Occurring DNA Modifications on DNA Structure and Packaging. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/289658
Chicago Manual of Style (16th Edition):
LI, ZHE. “Effect of Naturally Occurring DNA Modifications on DNA Structure and Packaging.” 2019. Doctoral Dissertation, University of Cambridge. Accessed January 17, 2021.
https://www.repository.cam.ac.uk/handle/1810/289658.
MLA Handbook (7th Edition):
LI, ZHE. “Effect of Naturally Occurring DNA Modifications on DNA Structure and Packaging.” 2019. Web. 17 Jan 2021.
Vancouver:
LI Z. Effect of Naturally Occurring DNA Modifications on DNA Structure and Packaging. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Jan 17].
Available from: https://www.repository.cam.ac.uk/handle/1810/289658.
Council of Science Editors:
LI Z. Effect of Naturally Occurring DNA Modifications on DNA Structure and Packaging. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://www.repository.cam.ac.uk/handle/1810/289658

University of Cambridge
2.
Li, Zhe.
Effect of naturally occurring DNA modifications on DNA structure and packaging.
Degree: PhD, 2019, University of Cambridge
URL: https://doi.org/10.17863/CAM.36906
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767744
► In eukaryotes, the genomic double-stranded DNA (dsDNA) coils around histones to form nucleosomes. Arrays of these nucleosomes bundle together to generate chromatin. Most DNA-related processes…
(more)
▼ In eukaryotes, the genomic double-stranded DNA (dsDNA) coils around histones to form nucleosomes. Arrays of these nucleosomes bundle together to generate chromatin. Most DNA-related processes require interactions between chromatin-protected DNA and cellular machinery. Access of cell machinery to genomic DNA is partially regulated by the position and stability of nucleosomes, which may be influenced by changes in nucleosomal DNA. DNA is composed of adenine (A), guanine (G), cytosine (C), thymine (T) nucleotides and their derivatives. It has been shown that some C derivatives participate in directing multiple biological processes, and aberrant modification patterns are often linked to diseases. It has been proposed that T derivatives exhibit similar effects. This thesis focuses on elucidating the effect of naturally occurring DNA modifications on the properties of dsDNA and nucleosomes. dsDNA sequences systematically modified with various T derivatives were characterized using classical biophysical techniques to assess the effect of these DNA modifications. The results indicate that in the sequence context studied, 5-hydroxymethyluracil modifications destabilize dsDNA, while dense symmetrical 5-formyluracil (fU) modifications alter the dsDNA structure. These effects may provide clues to the differential protein recruitment observed in previous research. In vitro studies on nucleosome occupancy and stability revealed that 5-formylcytosine (fC) modifications have positive effects on nucleosome formation and stability compared to the unmodified counterpart by influencing the intrinsic biochemical and biophysical properties of the nucleosomes. These results provide casual links for the observation in vivo between fC and the increased nucleosome occupancy and positioning. In order to further understand the positional effect of fC on the nucleosomes, a method was developed for quick and reliable incorporation of C derivatives into dsDNA at desired positions. The positive effect of fC modifications on nucleosome occupancy and stability observed here has necessitated further studies to gain deeper insights into the biological functions of fC in the nucleosome context. Cryo-EM can be used to elucidate the structural foundation for the changes fC posts to nucleosome, and protein interacting assays will identify the cellular machineries specifically recruited/repulsed by fC-modified nucleosomes. The effect of DNA modifications elucidated by the above studies advances our understanding on the role that DNA modifications play in regulating cellular processes.
Subjects/Keywords: nucleosome; DNA Modifications; DNA Structure; DNA Packaging
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Li, Z. (2019). Effect of naturally occurring DNA modifications on DNA structure and packaging. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.36906 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767744
Chicago Manual of Style (16th Edition):
Li, Zhe. “Effect of naturally occurring DNA modifications on DNA structure and packaging.” 2019. Doctoral Dissertation, University of Cambridge. Accessed January 17, 2021.
https://doi.org/10.17863/CAM.36906 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767744.
MLA Handbook (7th Edition):
Li, Zhe. “Effect of naturally occurring DNA modifications on DNA structure and packaging.” 2019. Web. 17 Jan 2021.
Vancouver:
Li Z. Effect of naturally occurring DNA modifications on DNA structure and packaging. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Jan 17].
Available from: https://doi.org/10.17863/CAM.36906 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767744.
Council of Science Editors:
Li Z. Effect of naturally occurring DNA modifications on DNA structure and packaging. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://doi.org/10.17863/CAM.36906 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767744

Oregon State University
3.
Kang, Hunseung.
Base inclinations for DNA in solutions and films as revealed by linear dichroism.
Degree: PhD, Biochemistry and Biophysics, 1993, Oregon State University
URL: http://hdl.handle.net/1957/35617
Subjects/Keywords: DNA – Structure
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kang, H. (1993). Base inclinations for DNA in solutions and films as revealed by linear dichroism. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/35617
Chicago Manual of Style (16th Edition):
Kang, Hunseung. “Base inclinations for DNA in solutions and films as revealed by linear dichroism.” 1993. Doctoral Dissertation, Oregon State University. Accessed January 17, 2021.
http://hdl.handle.net/1957/35617.
MLA Handbook (7th Edition):
Kang, Hunseung. “Base inclinations for DNA in solutions and films as revealed by linear dichroism.” 1993. Web. 17 Jan 2021.
Vancouver:
Kang H. Base inclinations for DNA in solutions and films as revealed by linear dichroism. [Internet] [Doctoral dissertation]. Oregon State University; 1993. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/1957/35617.
Council of Science Editors:
Kang H. Base inclinations for DNA in solutions and films as revealed by linear dichroism. [Doctoral Dissertation]. Oregon State University; 1993. Available from: http://hdl.handle.net/1957/35617
4.
Khuu, Patricia A.
Analyses of noncanonical DNA structures.
Degree: PhD, Biochemistry and Biophysics, 2008, Oregon State University
URL: http://hdl.handle.net/1957/8961
► The structural polymorphic nature of DNA has been long been recognized since the model of the right-handed B-DNA duplex proposed by James Watson and Francis…
(more)
▼ The structural polymorphic nature of
DNA has been long been recognized since the model of the right-handed B-
DNA duplex proposed by James Watson and Francis Crick was accepted. Its malleability is thought to be critical in protein recognition and manipulation. In particular, it can form Holliday junctions, four-way
DNA structural intermediates of homologous recombination mediated events in which four nucleic acid strands complex to give rise to double-helical arms extending from a central point. The variable recognition specificities of resolvases, a group of proteins that dissociate Holliday junctions into discrete duplexes, are addressed in this dissertation as related to the different structural conformations that can be adopted by junctions. We also describe an unusual base pair observed in the crystal
structure of a Holliday junction. The wobbled adenine-thymine base pair can be best ascribed to the assumption of a rare tautomeric form by one of the bases. Such observation provides unique and physiologically relevant evidence for a rare
nucleotide base tautomerization, with profound biological and chemical implications that deserve further investigation.
Finally, the evolutionary emergence of another known
DNA structure, the left-handed Z-
DNA, is also studied along with three other GC-rich genomic elements. The possible functions of Z-
DNA have only been recently elucidated though it was the first single-crystal X-ray
structure of a
DNA double helix. In our phylogenomic analysis of the genomes of sixteen organisms, ranging from cyanobacteria to complex eukaryotes, we offer new insights into its evolutionary emergence near the transcription start site. A model is derived which correlates its emergence with other transcriptional regulatory sequences and evolutionary gain of function. Thus, the studies presented in this thesis expand our knowledge of noncanonical
DNA structures and provoke questions about their functions in the cell.
Advisors/Committee Members: Ho, Pui Shing (advisor), Schimerlik, Michael I. (committee member).
Subjects/Keywords: DNA structure; DNA – Structure
…induced A•T wobble at the terminal base
pair of a crystal structure of Z-DNA… …who proposed that DNA exists as a helical secondary structure
comprised of two complementary… …x29;.
Since the Watson and Crick (W-C) structure, denoted as B-DNA or the B
form… …pairings and B-DNA double helix
structure remain the standard, studies reveal that the bases are… …to characterize the Holliday junction
intermediate and how this DNA structure is recognized…
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Khuu, P. A. (2008). Analyses of noncanonical DNA structures. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/8961
Chicago Manual of Style (16th Edition):
Khuu, Patricia A. “Analyses of noncanonical DNA structures.” 2008. Doctoral Dissertation, Oregon State University. Accessed January 17, 2021.
http://hdl.handle.net/1957/8961.
MLA Handbook (7th Edition):
Khuu, Patricia A. “Analyses of noncanonical DNA structures.” 2008. Web. 17 Jan 2021.
Vancouver:
Khuu PA. Analyses of noncanonical DNA structures. [Internet] [Doctoral dissertation]. Oregon State University; 2008. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/1957/8961.
Council of Science Editors:
Khuu PA. Analyses of noncanonical DNA structures. [Doctoral Dissertation]. Oregon State University; 2008. Available from: http://hdl.handle.net/1957/8961

University of Victoria
5.
Faris, Jonathan Scott.
Characterization of the DNA binding properties of the thyroid hormone receptor.
Degree: Department of Biochemistry and Microbiology, 2018, University of Victoria
URL: https://dspace.library.uvic.ca//handle/1828/9701
► This thesis describes work done with the thyroid hormone receptor (TR), a nuclear protein which binds to specific DNA sequences and regulates transcription in response…
(more)
▼ This thesis describes work done with the thyroid hormone receptor (TR), a nuclear
protein which binds to specific
DNA sequences and regulates transcription in response to
thyroid hormone levels. The studies can be divided into two broad categories:
structure/function studies of the TR protein, particularly with regards to
DNA binding
function; and,
structure/function studies of the
DNA sequences to which the thyroid
hormone receptor binds in order to regulate gene transcription.
In order to examine the
DNA binding properties of the TR an electrophoretic mobility
shift assay (EMSA) was utilized. Conditions of this assay were optimized for the use of in
vitro translated TR. Mutant forms of the β-isoform of thyroid hormone receptor were
generated using a PCR-based mutagenesis protocol. Each mutant substituted a different
residue of the 12 amino acid-long α-recognition helix with alanine. The mutants were
analyzed for their abilities to bind to thyroid hormone response elements (TREs), and to
activate transcription in transfected eukaryotic cells. The
DNA binding results were
consistent with a conserved α-helix
structure, with conserved function for many residues,
that is similar to that of the related receptors for glucocorticoids and estrogen. Only the first
of the three non-conserved residues lying in the P-box (EGG), a portion of the recognition
α-helix that facilitate differential binding of distinct
DNA sequences, disrupted binding
when substituted with alanine. The third position of the P-box, when substituted with
alanine exhibits an altered ability to bind to certain natural TREs. The mutant form of TR
with alanine substituted for the second P-box position displayed only a modest decrease in
DNA binding affinity compared to wild-type TR (roughly 3-fold), yet was completely
deficient in trans-activation.
The
structure-function studies of TR binding sites on
DNA applied a methylation
interference protocol to examine the interactions of TR with direct repeats (DR) of the
idealized hexameric sequence, spaced by three to five base-pairs. The interactions of both
the TR/TR homodimer and the TR/RXR (9-cis-retinoic acid receptor) heterodimer with the
DRs were examined. The methylation interference patterns for the TR/TR homodimer
bound to the DR sequences are virtually identical for spacers of four and five base-pairs,
but with three base-pairs, there is some evidence that at least one
DNA binding domain is
misaligned with the
DNA to accomodate the unfavourable spacer length. The TR/RXR
heterodimer methylation interference pattern is distinct on all three DRs, probably due to the
fact that in the heterodimer cooperative intermolecular contacts are made between the
DNA
binding domains of the two receptors, but only when the spacer distance is four base-pairs.
When a poorly conserved everted repeat (EvR) that overlaps the idealized DR is present.
the homodimer, but not the heterodimer, binds this cryptic EvR in competition with the
DR. The binding modality of the TR homodimer and TR/RXR…
Advisors/Committee Members: Romaniuk, Paul John (supervisor).
Subjects/Keywords: DNA; Structure; Nucleoproteins; Structure-activity relationships; DNA-protein interactions; Thyroid hormones
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Faris, J. S. (2018). Characterization of the DNA binding properties of the thyroid hormone receptor. (Thesis). University of Victoria. Retrieved from https://dspace.library.uvic.ca//handle/1828/9701
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Faris, Jonathan Scott. “Characterization of the DNA binding properties of the thyroid hormone receptor.” 2018. Thesis, University of Victoria. Accessed January 17, 2021.
https://dspace.library.uvic.ca//handle/1828/9701.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Faris, Jonathan Scott. “Characterization of the DNA binding properties of the thyroid hormone receptor.” 2018. Web. 17 Jan 2021.
Vancouver:
Faris JS. Characterization of the DNA binding properties of the thyroid hormone receptor. [Internet] [Thesis]. University of Victoria; 2018. [cited 2021 Jan 17].
Available from: https://dspace.library.uvic.ca//handle/1828/9701.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Faris JS. Characterization of the DNA binding properties of the thyroid hormone receptor. [Thesis]. University of Victoria; 2018. Available from: https://dspace.library.uvic.ca//handle/1828/9701
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
6.
NC DOCKS at The University of North Carolina at Greensboro; Proctor, Nathanael K.
Studying the effects of DNA methylation on adduct formation using molecular modeling.
Degree: 2011, NC Docks
URL: http://libres.uncg.edu/ir/uncg/f/Proctor_uncg_0154M_10650.pdf
► The goal of this study was to use molecular modeling to compare and analyze the molecular structure of a double-stranded DNA fragment, and the effects…
(more)
▼ The goal of this study was to use molecular modeling to compare and
analyze the molecular structure of a double-stranded DNA fragment, and the effects of DNA methylation to adduct formation, which may eventually lead to disease-related genetic mutations. Specifically, the research work in this thesis focuses on using molecular modeling to simulate the experimental results in a recent report in which DNA adduction occurs with BPDE (benzo[a]pyrene diol epoxide) within a specific double-stranded DNA fragment that contained various methylation patterns and was quantitatively measured. The ability to use molecular modeling to correlate the pattern of DNA methylation and the locations of the most frequent adduction sites with genotoxic compounds can be very useful to further advance the study of genetic mutation, prevention of diseases, and so on. In this study the MMFF94s force field was used to run molecular dynamics simulations on dsDNA, and the results were analyzed to determine changes in the rotation of specific base pairs and the distances between the base pairs as a result of DNA methylation. The results show that there is a significant change in those two characteristics between non-methylated DNA and methylated DNA which might lead to adduct formation with BPDE.
Subjects/Keywords: Adducts, DNA; DNA $x Structure; DNA $x Methylation
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
NC DOCKS at The University of North Carolina at Greensboro; Proctor, N. K. (2011). Studying the effects of DNA methylation on adduct formation using molecular modeling. (Thesis). NC Docks. Retrieved from http://libres.uncg.edu/ir/uncg/f/Proctor_uncg_0154M_10650.pdf
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
NC DOCKS at The University of North Carolina at Greensboro; Proctor, Nathanael K. “Studying the effects of DNA methylation on adduct formation using molecular modeling.” 2011. Thesis, NC Docks. Accessed January 17, 2021.
http://libres.uncg.edu/ir/uncg/f/Proctor_uncg_0154M_10650.pdf.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
NC DOCKS at The University of North Carolina at Greensboro; Proctor, Nathanael K. “Studying the effects of DNA methylation on adduct formation using molecular modeling.” 2011. Web. 17 Jan 2021.
Vancouver:
NC DOCKS at The University of North Carolina at Greensboro; Proctor NK. Studying the effects of DNA methylation on adduct formation using molecular modeling. [Internet] [Thesis]. NC Docks; 2011. [cited 2021 Jan 17].
Available from: http://libres.uncg.edu/ir/uncg/f/Proctor_uncg_0154M_10650.pdf.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
NC DOCKS at The University of North Carolina at Greensboro; Proctor NK. Studying the effects of DNA methylation on adduct formation using molecular modeling. [Thesis]. NC Docks; 2011. Available from: http://libres.uncg.edu/ir/uncg/f/Proctor_uncg_0154M_10650.pdf
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Indian Institute of Science
7.
Marathe, Arvind.
Intrinsic Versus Induced Variations In DNA Structure.
Degree: PhD, Faculty of Science, 2011, Indian Institute of Science
URL: http://etd.iisc.ac.in/handle/2005/1303
► The binding of different proteins involved in processes such as transcription, replication and chromatin compaction to regions of the genome is regulated by the structure…
(more)
▼ The binding of different proteins involved in processes such as transcription, replication and chromatin compaction to regions of the genome is regulated by the
structure of
DNA. Thus,
DNA structure acts as the crucial link modulating evolutionary selection of the
DNA sequence based on its own function, and the function of the proteins it encodes. The aim of this work is to examine the role of intrinsic, sequence-dependent structural variations vis-a -vis the protein-induced variations, in allowing
DNA to assume geometries necessary for binding by proteins. For this purpose, we carried out analyses of datasets of X-ray crystal structures of free and protein-bound
DNA, and molecular dynamics simulation studies of few free
DNA structures and a protein-
DNA complex. Each of the projects described below will appear as a separate chapter in the thesis.
Analysis of X-ray crystal
structure datasets
Dataset of high-resolution X-ray crystal structures of free and protein-bound
DNA
This project was initiated with the aim of investigating the variation in A-and B-forms of
DNA and the role they play in the binding of proteins. However, a survey of the existing literature indicated that the terms ‘A-DNA’ and ‘B-DNA’ were being used rather loosely and several different parameters at the local structural level were being used by various investigators to characterise these structures. Hence a systematic study was taken up to analyse all high-resolution free
DNA structures comprising of sufficient number of contiguous Watson-Crick basepairs, irrespective of how they were classified by the existing databases. We also carried out a study of double-helical, Watson-Crick basepaired, free RNA structures for comparison. The structures in the RNA dataset were observed to rigidly assume the A-form and hence the average values of different parameters for that dataset were used to characterise the A-form. The analysis of free
DNA and RNA structures was accompanied by an analysis of protein-bound
DNA crystal structures.
DNA structures bound to the helix-turn-helix motif in proteins were also analysed separately.
The analysis of free
DNA and RNA structures allowed us to pinpoint the parameters suitable for discriminating A-and B-forms of
DNA at the local structural level. The results illustrated that the free
DNA molecule, even in the crystalline state, samples a large amount of conformational space, encompassing both the A-and the B-forms. Most protein-bound
DNA structures, including those with large, smooth curvature, were observed to assume the B-form. The A-form was observed to be limited to a small number of dinucleotide steps in
DNA structures bound to the proteins belonging to a few specific families. Thus our study highlighted the structural versatility of B-form
DNA, which allowed it to take up a range of global geometries to accommodate most
DNA-binding protein motifs.
Dataset of X-ray crystal structures of the nucleosome
The study of high-resolution structures of free and protein-bound
DNA was followed by an analysis of a…
Advisors/Committee Members: Bansal, Manju (advisor).
Subjects/Keywords: DNA - Molecular Structure; DNA Binding Proteins; Protein-DNA Complex; Molecular Dynamics - Simulation; DNA Structures; DNA - Molecular Dynamics; Protein-Bound DNA; DNA - Crystal Structure; DNA Geometries; Biochemical Genetics
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Marathe, A. (2011). Intrinsic Versus Induced Variations In DNA Structure. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/1303
Chicago Manual of Style (16th Edition):
Marathe, Arvind. “Intrinsic Versus Induced Variations In DNA Structure.” 2011. Doctoral Dissertation, Indian Institute of Science. Accessed January 17, 2021.
http://etd.iisc.ac.in/handle/2005/1303.
MLA Handbook (7th Edition):
Marathe, Arvind. “Intrinsic Versus Induced Variations In DNA Structure.” 2011. Web. 17 Jan 2021.
Vancouver:
Marathe A. Intrinsic Versus Induced Variations In DNA Structure. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2011. [cited 2021 Jan 17].
Available from: http://etd.iisc.ac.in/handle/2005/1303.
Council of Science Editors:
Marathe A. Intrinsic Versus Induced Variations In DNA Structure. [Doctoral Dissertation]. Indian Institute of Science; 2011. Available from: http://etd.iisc.ac.in/handle/2005/1303

University of Manchester
8.
Shaw, Alexander George.
Developing Models of the Mammalian Cell S
Phase.
Degree: 2011, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:118561
► The accurate replication of the mammalian genome is a complex and logistically challenging process. The entirety of the genome must undergo a single duplication with…
(more)
▼ The accurate replication of the mammalian genome is
a complex and logistically challenging process. The entirety of the
genome must undergo a single duplication with as little error as
possible. This must occur in a coordinated fashion and over
suitably short time scale so as to allow timely cellular division
within a cell cycle that is typically around 24 hours in a human
cell. A great wealth of knowledge already exists describing various
aspects of the S phase, during which this replication of the genome
occurs. This data has been gathered over a variety of model
systems, ranging from inferences from the replicative mechanics of
SV40 through to direct observations of replication in mammalian
cells.In order integrate this data and determine the value of
inferences from different data sources, quantitative models of the
mammalian cell S phase are required. This study documents the
development of several such models and the exploration of the
influences that experimentally determined parameters and different
mechanistic theories can have on the behaviour of a simulated S
phase. Of particular exploratory interest were the modes of
activating replication of replicon clusters, with the aim of
simulating experimentally observed dynamics. Additionally, the
study also aimed to investigate the variation of replication fork
rates and the density of origins of replication, along with the
relationship that occurs between the two during both replicational
stress and during a normal S phase. Through an iterative series of
models, relevant parameters and key theories are sequentially
explored so as to better understand the S phase. Particularly
influential parameters were identified and studied in detail, with
experimental determination where necessary in order to more
accurately inform the model system. Conclusions concerning the
behaviour of the system and the potential impact of the results
were drawn upon the completion of each level of modelling and
experimental work.To conclude the study, a linear model simulating
the genome of the MRC5 cell line was used to estimate the modes
activation of
DNA replication along chromosomes in order to
recreate experimentally observed replication dynamics.
Experimentally determined profiles of replication fork rates and
the density of origin firing were also determined for the MRC5 cell
line, and were used to populate the model with accurate and
appropriate data. Using the model to simulate S phase through a
variety of behavioural parameters, realistic S phase dynamics were
found to occur through a combination of de novo activation of
replicon clusters and a specific probability of neighbour
activation by completed clusters. These derived mechanics, when
performed on a system correctly parameterised with suitable data,
can simulate experimentally observed phenomena. The development of
the model highlighted the requirements of data fit for purpose, and
the study also stresses the need for critical consideration of
inferences made between different model systems.
Advisors/Committee Members: BAIER, GEROLD G, Jackson, Dean, Baier, Gerold.
Subjects/Keywords: DNA Replication; Modelling; Mammalian cells; Nuclear Structure
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shaw, A. G. (2011). Developing Models of the Mammalian Cell S
Phase. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:118561
Chicago Manual of Style (16th Edition):
Shaw, Alexander George. “Developing Models of the Mammalian Cell S
Phase.” 2011. Doctoral Dissertation, University of Manchester. Accessed January 17, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:118561.
MLA Handbook (7th Edition):
Shaw, Alexander George. “Developing Models of the Mammalian Cell S
Phase.” 2011. Web. 17 Jan 2021.
Vancouver:
Shaw AG. Developing Models of the Mammalian Cell S
Phase. [Internet] [Doctoral dissertation]. University of Manchester; 2011. [cited 2021 Jan 17].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:118561.
Council of Science Editors:
Shaw AG. Developing Models of the Mammalian Cell S
Phase. [Doctoral Dissertation]. University of Manchester; 2011. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:118561

Boston University
9.
Azad, Robert Navid.
Hydroxyl radical cleavage of nucleic acids: understanding RNA cleavage profiles and identifying DNA structural motifs.
Degree: PhD, Chemistry, 2014, Boston University
URL: http://hdl.handle.net/2144/15123
► High-resolution techniques to characterize the three-dimensional structure of nucleic acids are critical for understanding the mechanisms of action of biologically important RNA and DNA molecules.…
(more)
▼ High-resolution techniques to characterize the three-dimensional structure of nucleic acids are critical for understanding the mechanisms of action of biologically important RNA and DNA molecules. Methods based on chemical probing have been particularly useful in gaining insight into the structures of nucleic acids in solution. The hydroxyl radical has been widely adopted as a chemical probe for DNA and RNA structure since its first application to protein-DNA footprinting. This dissertation describes efforts to improve upon the current model of how the hydroxyl radical cleaves the RNA backbone, through the use of specifically deuterated ribonucleoside triphosphates (NTPs). The synthesis and purification of deuterated NTPs are described in detail, as well as their application to the study of two RNAs: the sarcin-ricin loop (SRL) RNA - a biologically active region of ribosomal RNA - and a short RNA designed to lack secondary structure. Measurement of deuterium kinetic isotope effects (KIEs) on the cleavage of these RNAs suggests that it is possible to use this experiment to identify the GUA base triple structural motif that is commonly found in RNA.
Abstraction of a 5' ribose hydrogen atom in RNA yields a fragment containing a 5'-aldehyde terminus with the sugar and base intact. Comparison of primer extension products of cleaved SRL RNA with or without deuterium substituted at the C5' ribose position of uracil residues demonstrated that the 5' aldehyde-terminated fragment can serve as a template for reverse transcription. Implications of the presence of a 5'-aldehyde terminus on hydroxyl radical cleavage analysis are discussed in the context of reverse transcriptase-mediated primer extension, a commonly used method.
Structural features of naked DNA molecules with known protein binding sequences were explored using hydroxyl radical cleavage analyzed by capillary gel electrophoresis. An application was written in MATLAB to deconvolute and integrate cleavage intensities of hundreds of peaks in an electropherogram. In many cases, comparison of the cleavage profile to the minor groove width found in an X-ray co-crystal structure of the DNA-protein complex revealed a high degree of correlation.
Subjects/Keywords: Chemistry; DNA; RNA; Hydroxyl; Probing; Radical; Structure
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Azad, R. N. (2014). Hydroxyl radical cleavage of nucleic acids: understanding RNA cleavage profiles and identifying DNA structural motifs. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/15123
Chicago Manual of Style (16th Edition):
Azad, Robert Navid. “Hydroxyl radical cleavage of nucleic acids: understanding RNA cleavage profiles and identifying DNA structural motifs.” 2014. Doctoral Dissertation, Boston University. Accessed January 17, 2021.
http://hdl.handle.net/2144/15123.
MLA Handbook (7th Edition):
Azad, Robert Navid. “Hydroxyl radical cleavage of nucleic acids: understanding RNA cleavage profiles and identifying DNA structural motifs.” 2014. Web. 17 Jan 2021.
Vancouver:
Azad RN. Hydroxyl radical cleavage of nucleic acids: understanding RNA cleavage profiles and identifying DNA structural motifs. [Internet] [Doctoral dissertation]. Boston University; 2014. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/2144/15123.
Council of Science Editors:
Azad RN. Hydroxyl radical cleavage of nucleic acids: understanding RNA cleavage profiles and identifying DNA structural motifs. [Doctoral Dissertation]. Boston University; 2014. Available from: http://hdl.handle.net/2144/15123

Montana State University
10.
Remington, Jacob Michael.
Fluorescence quenching in 2-aminopurine-labeled model DNA systems.
Degree: PhD, College of Letters & Science, 2019, Montana State University
URL: https://scholarworks.montana.edu/xmlui/handle/1/15563
► For the last 50 years changes to the fluorescence properties of 2-aminopurine have been used to probe the structure and dynamics of DNA. 2-Aminopurine's utility…
(more)
▼ For the last 50 years changes to the fluorescence properties of 2-aminopurine have been used to probe the
structure and dynamics of
DNA. 2-Aminopurine's utility has arisen from the quenching of its emission when pi-stacked with neighboring nucleobases. In the time-domain, the emission decay profile of 2-aminopurine requires multiple exponential decay components to model. Despite its extensive usage, the microscopic origin of the decay heterogeneity is not clear. In this thesis, steady-state absorption, fluorescence, and time-resolved fluorescence results are compared to multiple microsecond molecular dynamics simulations of 2-aminopurine-labeled adenine containing single-stranded
DNA oligomers of varying length and position of the 2-aminopurine probe. First, previous reports of ultrafast electron transfer in pi-stacked adenine oligomers are used to build a new model for quenching of 2-aminopurine that is pi-stacked with adenine. For dinucleotides, a static distribution of unstacked structures combined with a distance dependent electron transfer mechanism is posited to explain the disperse emission decay timescales. Investigating the dinucleotides with molecular dynamics simulations analyzed with Markov state models quantify the structural heterogeneity of the dinucleotides. At least seven structures are sampled that could alter the quenching of 2-aminopurines's fluorescence. The Markov state models also demonstrate the timescales for transitions between these structures range from 1.6 to 25 ns, suggesting 2-aminopurine, with its monomer-like lifetime of 10 ns, is sensitive to the conformational dynamics of the dinucleotides as well. This dual fluorescence quenching and molecular dynamics simulation approach is extended to 2-aminopurine labeled trinucleotides and 15 base oligomers to interrogate the position dependent structural heterogeneity and conformational dynamics in these systems. Both shifts in the experimental absorption spectra, and molecular dynamics simulations agree that the interior base is more likely to be stacked than the exterior bases. Time-resolved emission experiments reveal emission from 2-aminopurine is quenched faster on the 5' end relative to the 3' end, in agreement with the faster stacking kinetics observed for bases on the 5' end relative to the 3' end obtained from molecular dynamics simulation. These results suggest that the time-resolved emission from 2-aminopurine may serve as an experimental observable for calibration of the dynamical properties predicted by molecular dynamics simulation.
Advisors/Committee Members: Chairperson, Graduate Committee: Patrik R. Callis (advisor), Abbey M. Philip, Mahesh Hariharan and Bern Kohler were co-authors of the article, 'On the origin of multiexponential fluorescence decays from 2-aminopurine labeled dinucleotides' in the journal 'The journal of chemical physics' which is contained within this thesis. (other), Martin McCullagh and Bern Kohler were co-authors of the article, 'Molecular dynamics simulations of 2-aminopurine-labeled dinucleoside monophosphates reveal multiscale stacking kinetics' in the journal 'Journal of physical chemistry B' which is contained within this thesis. (other).
Subjects/Keywords: Fluorescence.; DNA.; Molecular dynamics.; Molecular structure.; Nucleotides.
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Remington, J. M. (2019). Fluorescence quenching in 2-aminopurine-labeled model DNA systems. (Doctoral Dissertation). Montana State University. Retrieved from https://scholarworks.montana.edu/xmlui/handle/1/15563
Chicago Manual of Style (16th Edition):
Remington, Jacob Michael. “Fluorescence quenching in 2-aminopurine-labeled model DNA systems.” 2019. Doctoral Dissertation, Montana State University. Accessed January 17, 2021.
https://scholarworks.montana.edu/xmlui/handle/1/15563.
MLA Handbook (7th Edition):
Remington, Jacob Michael. “Fluorescence quenching in 2-aminopurine-labeled model DNA systems.” 2019. Web. 17 Jan 2021.
Vancouver:
Remington JM. Fluorescence quenching in 2-aminopurine-labeled model DNA systems. [Internet] [Doctoral dissertation]. Montana State University; 2019. [cited 2021 Jan 17].
Available from: https://scholarworks.montana.edu/xmlui/handle/1/15563.
Council of Science Editors:
Remington JM. Fluorescence quenching in 2-aminopurine-labeled model DNA systems. [Doctoral Dissertation]. Montana State University; 2019. Available from: https://scholarworks.montana.edu/xmlui/handle/1/15563

Duke University
11.
Zhou, Huiqing.
Occurrence and Function of Hoogsteen Base Pairs in Nucleic Acids
.
Degree: 2016, Duke University
URL: http://hdl.handle.net/10161/12892
► Nucleic acids (DNA and RNA) play essential roles in the central dogma of biology for the storage and transfer of genetic information. The unique…
(more)
▼ Nucleic acids (
DNA and RNA) play essential roles in the central dogma of biology for the storage and transfer of genetic information. The unique chemical and conformational structures of nucleic acids – the double helix composed of complementary Watson-Crick base pairs, provide the structural basis to carry out their biological functions.
DNA double helix can dynamically accommodate Watson-Crick and Hoogsteen base-pairing, in which the purine base is flipped by ~180° degrees to adopt syn rather than anti conformation as in Watson-Crick base pairs. There is growing evidence that Hoogsteen base pairs play important roles in
DNA replication, recognition, damage or mispair accommodation and repair. Here, we constructed a database for existing Hoogsteen base pairs in
DNA duplexes by a
structure-based survey from the Protein Data Bank, and structural analyses based on the resulted Hoogsteen structures revealed that Hoogsteen base pairs occur in a wide variety of biological contexts and can induce
DNA kinking towards the major groove. As there were documented difficulties in modeling Hoogsteen or Watson-Crick by crystallography, we collaborated with the Richardsons’ lab and identified potential Hoogsteen base pairs that were mis-modeled as Watson-Crick base pairs which suggested that Hoogsteen can be more prevalent than it was thought to be. We developed solution NMR method combined with the site-specific isotope labeling to characterize the formation of, or conformational exchange with Hoogsteen base pairs in large
DNA-protein complexes under solution conditions, in the absence of the crystal packing force. We showed that there are enhanced chemical exchange, potentially between Watson-Crick and Hoogsteen, at a sharp kink site in the complex formed by
DNA and the Integration Host Factor protein. In stark contrast to B-form
DNA, we found that Hoogsteen base pairs are strongly disfavored in A-form RNA duplex. Chemical modifications N1-methyl adenosine and N1-methyl guanosine that block Watson-Crick base-pairing, can be absorbed as Hoogsteen base pairs in
DNA, but rather potently destabilized A-form RNA and caused helix melting. The intrinsic instability of Hoogsteen base pairs in A-form RNA endows the N1-methylation as a functioning post-transcriptional modification that was known to facilitate RNA folding, translation and potentially play roles in the epitranscriptome. On the other hand, the dynamic property of
DNA that can accommodate Hoogsteen base pairs could be critical to maintaining the genome stability.
Advisors/Committee Members: Al-Hashimi, Hashim M (advisor).
Subjects/Keywords: Biochemistry;
DNA;
Hoogsteen;
RNA;
solution NMR;
structure
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhou, H. (2016). Occurrence and Function of Hoogsteen Base Pairs in Nucleic Acids
. (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/12892
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zhou, Huiqing. “Occurrence and Function of Hoogsteen Base Pairs in Nucleic Acids
.” 2016. Thesis, Duke University. Accessed January 17, 2021.
http://hdl.handle.net/10161/12892.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zhou, Huiqing. “Occurrence and Function of Hoogsteen Base Pairs in Nucleic Acids
.” 2016. Web. 17 Jan 2021.
Vancouver:
Zhou H. Occurrence and Function of Hoogsteen Base Pairs in Nucleic Acids
. [Internet] [Thesis]. Duke University; 2016. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/10161/12892.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zhou H. Occurrence and Function of Hoogsteen Base Pairs in Nucleic Acids
. [Thesis]. Duke University; 2016. Available from: http://hdl.handle.net/10161/12892
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Hong Kong University of Science and Technology
12.
Lin, Tong CBME.
Self-assembly and reconfigurations of complex DNA nanostructures from the preformed structural units and DNA devices for bioengineering applications.
Degree: 2018, Hong Kong University of Science and Technology
URL: http://repository.ust.hk/ir/Record/1783.1-104947
;
https://doi.org/10.14711/thesis-991012634869203412
;
http://repository.ust.hk/ir/bitstream/1783.1-104947/1/th_redirect.html
► Structural DNA nanotechnology has been advanced in an extraordinary pace in the past three decades and increasingly more complex structures have been demonstrated in the…
(more)
▼ Structural DNA nanotechnology has been advanced in an extraordinary pace in the past three decades and increasingly more complex structures have been demonstrated in the field based on the three major categories of structural units: DNA branched junction, DNA origami and SSTs. Overall, they have been developed as very handy tools in bioengineering applications. One of the major challenges is to further scale up the self-assembly to build structures of expanded sizes and thus higher complexity. There are a number of ways to scale up DNA self-assembly, and the most direct one is to use a longer scaffold in origami approach; or in scaffold-free approach to increase the number of component species. However, it is not always convenient to obtain a long enough scaffold with satisfactory quality; and increasing number of component species can lead to an exponential drop in self-assembly yield. Hence, instead of one-pot self-assembly, higher-ordered structures can also be constructed in hierarchy from preformed structural units by either (i) sticky-end association, (ii) shape complementarity with blunt-end stacking, (iii) or the guidance from scaffold. Here, we demonstrated a new method, through the sticky-end association and toehold-mediated strand displacement, to form DNA nanostructures of higher order from the preformed SSTs. For bioengineering applications, DNA nanostructures must meet several essential criteria: (i) programmability, each component tile can be independently included, removed or modified. (ii) simplicity, the assembly and disassembly must be rather simple and easy-to-implement. (iii) reversibility, the assembly and disassembly must be switchable and inducible. Therefore, SSTs can be a promising solution. Here, we demonstrated the ability to reconfigure the preformed DNA nanostructures, through the toehold-mediated strand displacement, into complex 2D and 3D conformations in a switchable and inducible manner. We also created complex DNA nanostructures for bioengineering applications: one 2D system to immobilize, target and image molecules of interest and one 3D system to detect, bind, protect and deliver specific molecules to their destinations.
Subjects/Keywords: DNA
; Structure
; Nanochemistry
; Self-assembly (Chemistry)
; Bioengineering
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lin, T. C. (2018). Self-assembly and reconfigurations of complex DNA nanostructures from the preformed structural units and DNA devices for bioengineering applications. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-104947 ; https://doi.org/10.14711/thesis-991012634869203412 ; http://repository.ust.hk/ir/bitstream/1783.1-104947/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lin, Tong CBME. “Self-assembly and reconfigurations of complex DNA nanostructures from the preformed structural units and DNA devices for bioengineering applications.” 2018. Thesis, Hong Kong University of Science and Technology. Accessed January 17, 2021.
http://repository.ust.hk/ir/Record/1783.1-104947 ; https://doi.org/10.14711/thesis-991012634869203412 ; http://repository.ust.hk/ir/bitstream/1783.1-104947/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lin, Tong CBME. “Self-assembly and reconfigurations of complex DNA nanostructures from the preformed structural units and DNA devices for bioengineering applications.” 2018. Web. 17 Jan 2021.
Vancouver:
Lin TC. Self-assembly and reconfigurations of complex DNA nanostructures from the preformed structural units and DNA devices for bioengineering applications. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2018. [cited 2021 Jan 17].
Available from: http://repository.ust.hk/ir/Record/1783.1-104947 ; https://doi.org/10.14711/thesis-991012634869203412 ; http://repository.ust.hk/ir/bitstream/1783.1-104947/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lin TC. Self-assembly and reconfigurations of complex DNA nanostructures from the preformed structural units and DNA devices for bioengineering applications. [Thesis]. Hong Kong University of Science and Technology; 2018. Available from: http://repository.ust.hk/ir/Record/1783.1-104947 ; https://doi.org/10.14711/thesis-991012634869203412 ; http://repository.ust.hk/ir/bitstream/1783.1-104947/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manchester
13.
Henthorn, Nicholas Thomas.
Modelling and Measurement of Simple and Complex DNA
Damage Induction by Ion Irradiation.
Degree: 2018, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:315268
► Photons have been used in radiotherapy for a number of years, and a lot of experience has been gained; experience which does not currently exist…
(more)
▼ Photons have been used in radiotherapy for a number
of years, and a lot of experience has been gained; experience which
does not currently exist for protons. In order to apply this
experience, and to optimise proton therapy, a dose conversion is
applied, known as the Relative Biological Effectiveness (RBE). A
constant RBE of 1.1 is in clinical use. However, a number of
experimental studies have shown that RBE is not constant; depending
on a number of factors, such as Linear Energy Transfer (LET), cell
type, and dose etc. The RBE of 1.1 is based on a number of in vitro
studies, however, within this data exists a significant variance.
It has been estimated that proton RBE ranges from around 1, at the
entrance, to around 2.5, at the distal edge. The value of 1.1 has
been clinically accepted as a “safe†value, with no signs of
significant under- or over-dosing. However, the open question of
RBE, and the biologically extended range, can lead to potential
degradation in treatment plan quality. For example, proton distal
edges are not placed near organs at risk, where RBE is highest. A
number of phenomenological models have been developed to
encapsulate variable RBE. These models link cell survival
parameters between photons and protons, with a scaling from LET.
However, the models are fit with the same in vitro data used to
derive RBE. The models also, by definition, give no information on
underlying mechanisms of variable RBE, aside from implicitly
stating that there is increased cell kill at increased LET. Noise
in the data used to fit the models could explain the lack of
clinical implementation. Mechanistically, it is believed that cell
kill is a result of
DNA damage and the efficacy of repair. In
particular, the induction of
DNA Double Strand Breaks (DSBs) has
been identified as the toxic mechanism. By simulating the process
of DSB induction and repair, mechanisms can be uncovered. This work
presents results of such a methodology. The mechanisms that lead to
direct and indirect
DNA damage are simulated, with parameters of
the mechanisms fit to experiments on
DNA extracts or parameters
taken from the literature. The mechanisms are applied to larger
biological systems, making predictions of
DNA damage at the
cellular level. Prediction of
DNA damage is correlated to
conventional units that can be scored in proton therapy, dose and
LET. This allows for the model predictions to be applied to
clinically relevant cases, such as in treatment planning software.
In all cases, the simulations predict an increase in yield,
complexity, and density of DSBs with LET. This translates to an
increase in misrepaired and residual DSBs, i.e. biological effect.
The work provides mechanisms for the experimentally observed
increase in cell kill with proton depth.
Advisors/Committee Members: MACKAY, RANALD RI, MERCHANT, MICHAEL M, Kirkby, Karen, Mackay, Ranald, Merchant, Michael.
Subjects/Keywords: Proton Therapy; Geant4-DNA; Monte Carlo Track Structure; DNA Damage; Radiotherapy
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Henthorn, N. T. (2018). Modelling and Measurement of Simple and Complex DNA
Damage Induction by Ion Irradiation. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:315268
Chicago Manual of Style (16th Edition):
Henthorn, Nicholas Thomas. “Modelling and Measurement of Simple and Complex DNA
Damage Induction by Ion Irradiation.” 2018. Doctoral Dissertation, University of Manchester. Accessed January 17, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:315268.
MLA Handbook (7th Edition):
Henthorn, Nicholas Thomas. “Modelling and Measurement of Simple and Complex DNA
Damage Induction by Ion Irradiation.” 2018. Web. 17 Jan 2021.
Vancouver:
Henthorn NT. Modelling and Measurement of Simple and Complex DNA
Damage Induction by Ion Irradiation. [Internet] [Doctoral dissertation]. University of Manchester; 2018. [cited 2021 Jan 17].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:315268.
Council of Science Editors:
Henthorn NT. Modelling and Measurement of Simple and Complex DNA
Damage Induction by Ion Irradiation. [Doctoral Dissertation]. University of Manchester; 2018. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:315268

Vanderbilt University
14.
Politica, Dustin Alan.
Structural Consequences of the C8-Guanine DNA Adduct Formed by 3-Nitrobenzanthrone; an Environmental Carcinogen.
Degree: PhD, Chemistry, 2016, Vanderbilt University
URL: http://hdl.handle.net/1803/13779
► Damage to DNA results from many endogenous and exogenous sources and plays a significant role in cancer etiology. 3-Nitrobenzathrone (3-NBA) is a component of diesel…
(more)
▼ Damage to
DNA results from many endogenous and exogenous sources and plays a significant role in cancer etiology. 3-Nitrobenzathrone (3-NBA) is a component of diesel exhaust that is known to form
DNA adducts. Aminobenzanthrone (ABA)
DNA adducts result through the reaction of electrophilic nitrenium ions formed during 3-NBA’s metabolic reduction in vivo. Furthermore, 3-NBA has been reported as being carcinogenic in animal model systems and human exposure has been demonstrated. Here I examine structural impacts of the C8-guanine-aminobenzanthrone (C8-dG-ABA) adduct, a major
DNA adduct of 3-NBA, which occurs at the C8 position of guanine. This adduct produced a base-displaced intercalated
structure within a
DNA duplex. The ABA moiety intercalated into the duplex displacing the cytosine opposite the lesion. The adducted guanine rotated about the glycosidic bond into the syn conformation. The overall stability of the
DNA duplex was reduced as demonstrated by a decrease in melting temperature of 11º C compared to the undamaged duplex. Another
structure was determined for C8-dG-ABA in complex with a trans-lesion synthesis polymerase, human polymerase eta (hPol η). The conformation of the C8-dG-ABA adduct within the active site of hPol η was markedly different from the
structure observed in duplex
DNA. The complex was captured in a non-mutagenic insertion state. The adducted guanine was in the anti conformation and was observed to form a Watson-Crick basepair with an incoming cytosine triphosphate (dCTP). The ABA moiety was rotated out of the active site of hPol η and resided in a hydrophobic pocket. The position of the ABA moiety did not allow for a clear path for the next template base to be translocated into the active site, and may reflect a means by which the adduct blocks replication.
Advisors/Committee Members: Martin Egli, Ph.D. (committee member), Jens Meiler, Ph.D. (committee member), Carmelo J. Rizzo, Ph.D. (committee member), Michael P. Stone, Ph.D. (Committee Chair).
Subjects/Keywords: DNA structure; DNA damage; Nitroaromatic; translesion synthesis; damage bypass; Nitroarene
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Politica, D. A. (2016). Structural Consequences of the C8-Guanine DNA Adduct Formed by 3-Nitrobenzanthrone; an Environmental Carcinogen. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/13779
Chicago Manual of Style (16th Edition):
Politica, Dustin Alan. “Structural Consequences of the C8-Guanine DNA Adduct Formed by 3-Nitrobenzanthrone; an Environmental Carcinogen.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed January 17, 2021.
http://hdl.handle.net/1803/13779.
MLA Handbook (7th Edition):
Politica, Dustin Alan. “Structural Consequences of the C8-Guanine DNA Adduct Formed by 3-Nitrobenzanthrone; an Environmental Carcinogen.” 2016. Web. 17 Jan 2021.
Vancouver:
Politica DA. Structural Consequences of the C8-Guanine DNA Adduct Formed by 3-Nitrobenzanthrone; an Environmental Carcinogen. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/1803/13779.
Council of Science Editors:
Politica DA. Structural Consequences of the C8-Guanine DNA Adduct Formed by 3-Nitrobenzanthrone; an Environmental Carcinogen. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/13779

Brno University of Technology
15.
Němec, Jiří.
Vyhledávání specifických sekundárních struktur v DNA sekvencích: Finding Specific Secondary Structures in DNA Sequences.
Degree: 2020, Brno University of Technology
URL: http://hdl.handle.net/11012/187409
► This Bachelor thesis is focused on analyse and design an algorithm for searching specific structure in DNA sequences, especially for detection of quadruplexes. Work objective…
(more)
▼ This Bachelor thesis is focused on analyse and design an algorithm for searching specific
structure in
DNA sequences, especially for detection of quadruplexes. Work objective is to design and implement an effective application with linear time complexity. Work includes description of searching and used algorithms including their complexity.
Advisors/Committee Members: Martínek, Tomáš (advisor), Burgetová, Ivana (referee).
Subjects/Keywords: DNA; sekundární struktura; kvadruplex; DNA; secondary structure; quadruplex
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Němec, J. (2020). Vyhledávání specifických sekundárních struktur v DNA sekvencích: Finding Specific Secondary Structures in DNA Sequences. (Thesis). Brno University of Technology. Retrieved from http://hdl.handle.net/11012/187409
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Němec, Jiří. “Vyhledávání specifických sekundárních struktur v DNA sekvencích: Finding Specific Secondary Structures in DNA Sequences.” 2020. Thesis, Brno University of Technology. Accessed January 17, 2021.
http://hdl.handle.net/11012/187409.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Němec, Jiří. “Vyhledávání specifických sekundárních struktur v DNA sekvencích: Finding Specific Secondary Structures in DNA Sequences.” 2020. Web. 17 Jan 2021.
Vancouver:
Němec J. Vyhledávání specifických sekundárních struktur v DNA sekvencích: Finding Specific Secondary Structures in DNA Sequences. [Internet] [Thesis]. Brno University of Technology; 2020. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/11012/187409.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Němec J. Vyhledávání specifických sekundárních struktur v DNA sekvencích: Finding Specific Secondary Structures in DNA Sequences. [Thesis]. Brno University of Technology; 2020. Available from: http://hdl.handle.net/11012/187409
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Wollongong
16.
Horan, Nicholas.
Investigations into the Architecture and Function of the Bacterial Replisome.
Degree: PhD, 2016, University of Wollongong
URL: 060106
Cellular
Interactions
(incl.
Adhesion,
Matrix,
Cell
Wall),
060107
Enzymes,
060112
Structural
Biology
(incl.
Macromolecular
Modelling)
;
https://ro.uow.edu.au/theses/4937
► The accurate and efficient replication of Escherichia coli DNA is catalysed by a 17‐subunit assembly of proteins termed the DNA polymerase III holoenzyme (Pol…
(more)
▼ The accurate and efficient replication of Escherichia coli DNA is catalysed by a 17‐subunit assembly of proteins termed the DNA polymerase III holoenzyme (Pol III HE). The Pol III HE is further organised into three sub‐assemblies: the clamp‐loader complex, the β2 sliding clamp and the Pol III core complex (Pol III core). The Pol III core is comprised of the α polymerase, the ε exonuclease and the small θ subunit of an as yet undefined function. The β2 subunit encircles dsDNA and locks the Pol III core onto a template DNA by interaction with clamp‐binding motifs (CBMs) located in the α and ε subunits.
A detailed understanding of how the β2αεθ complex interacts with DNA and transforms to accommodate both DNA synthesis and proofreading functions is of great interest to researchers in the field. In this project, I used a combination of experimental techniques including protein crystallography, small‐angle X‐ray scattering (SAXS), nuclear magnetic resonance (NMR) and a variety of additional biochemical methods to build and validate an atomic resolution model of the structure of the β2αεθ complex. I further investigated a strategy for the fluorescent labelling of Pol III core proteins for use in future single‐molecule experiments.
Subjects/Keywords: protein structure; DNA replication; Escherichia coli; DNA polymerase III
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Horan, N. (2016). Investigations into the Architecture and Function of the Bacterial Replisome. (Doctoral Dissertation). University of Wollongong. Retrieved from 060106 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall), 060107 Enzymes, 060112 Structural Biology (incl. Macromolecular Modelling) ; https://ro.uow.edu.au/theses/4937
Chicago Manual of Style (16th Edition):
Horan, Nicholas. “Investigations into the Architecture and Function of the Bacterial Replisome.” 2016. Doctoral Dissertation, University of Wollongong. Accessed January 17, 2021.
060106 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall), 060107 Enzymes, 060112 Structural Biology (incl. Macromolecular Modelling) ; https://ro.uow.edu.au/theses/4937.
MLA Handbook (7th Edition):
Horan, Nicholas. “Investigations into the Architecture and Function of the Bacterial Replisome.” 2016. Web. 17 Jan 2021.
Vancouver:
Horan N. Investigations into the Architecture and Function of the Bacterial Replisome. [Internet] [Doctoral dissertation]. University of Wollongong; 2016. [cited 2021 Jan 17].
Available from: 060106 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall), 060107 Enzymes, 060112 Structural Biology (incl. Macromolecular Modelling) ; https://ro.uow.edu.au/theses/4937.
Council of Science Editors:
Horan N. Investigations into the Architecture and Function of the Bacterial Replisome. [Doctoral Dissertation]. University of Wollongong; 2016. Available from: 060106 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall), 060107 Enzymes, 060112 Structural Biology (incl. Macromolecular Modelling) ; https://ro.uow.edu.au/theses/4937

Univerzitet u Beogradu
17.
Divac, Aleksandra, 1975-.
Promene strukture DNK izazvane proteinom
HsOrc4.
Degree: Biološki fakultet, 2018, Univerzitet u Beogradu
URL: https://fedorabg.bg.ac.rs/fedora/get/o:18975/bdef:Content/get
► Биологија/Молекуларна биологија ; Biology/Molecular biology
У ћелијама свих живих организама репликација ДНК се одвија у неколико сложених и међусобно веома сличних фаза, а започиње тек…
(more)
▼ Биологија/Молекуларна биологија ; Biology/Molecular
biology
У ћелијама свих живих организама репликација ДНК се
одвија у неколико сложених и међусобно веома сличних фаза, а
започиње тек када иницијаторни протеински комплекс препозна
специфичне секвенце у геному. И поред великог биолошког значаја
процеса репликације мало се зна о механизмима који регулишу
иницицијацију синтезе ДНК вишећелијских еукариота. Ори секвенце
ових организама не садрже консензус секвенце, али су богате АТ
базним паровима груписаним у кратке, наизменичне или хомогене
низове. Овакви елементи могу да формирају алтернативне структуре, а
оне могу бити значајне за интеракцију ори секвенци и иницијаторног
комплекса, или могу настати током интеракције иницијационог
комплекса и ДНК и бити значајне за наредне фазе иницијације. У овом
раду су испитиване интеракције рекомбинантног протеина HsOrc4 са
фрагментом изолованим из хуманог репликатора LMNB2 и различитим
синтетским ДНК које саджре А и Т елементе. Протеин је изабран за
анализу јер чини део комплекса ORC (eng. Origin Recognition
Complex), показује самосталну везивну активност и припада фамилији
ААА+ суперфамилије макромолекулских шаперона. У раду је потврђено
да се HsOrc4 преференцијално везује за ДНК богату АТ базним
паровима и ТАТ елементима, и показано да стимулише некакнонску
ренатурацију комплементарних фрагмената у специфичну троланчану
структуру. Такође је показано да овај протеин стимулише и формирање
ТАТ триплекса од одговарајућих олигонуклеотида. У раду је описана и
сасвим неочекивана способност протеина да катализује асоцијацију
хомоаденинских олигонуклеотида у раније непознате дволанчане и,
вероватно, четвороланчане структуре. Хомоаденинске структуре биле
су зависне од магнезијумових јона, термостабилне и повезане
Хугстиновим везама. Судећи према деловању мутираних форми протеинa
HsOrc4 неактивних у везивању или хидролизи АТР-а, за каталитичку
активност HsOrc4 неопходно је везивање, али не и хидролиза АТР-а.
Будући да је основна улога иницијационог комплекса да ремоделује
ори секвенцу и припреми је за наредне фазе иницијације, описано
деловање протеина HsOrc4 могло би да допринесе формирању комплексне
архитектуре ори репликације и да има значајну улогу у иницијацији
репликације.
Subjects/Keywords: DNA structure; DNA triplex; origin of replication; ORC
complex; HsOrc4 protein
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Divac, Aleksandra, 1. (2018). Promene strukture DNK izazvane proteinom
HsOrc4. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:18975/bdef:Content/get
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Divac, Aleksandra, 1975-. “Promene strukture DNK izazvane proteinom
HsOrc4.” 2018. Thesis, Univerzitet u Beogradu. Accessed January 17, 2021.
https://fedorabg.bg.ac.rs/fedora/get/o:18975/bdef:Content/get.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Divac, Aleksandra, 1975-. “Promene strukture DNK izazvane proteinom
HsOrc4.” 2018. Web. 17 Jan 2021.
Vancouver:
Divac, Aleksandra 1. Promene strukture DNK izazvane proteinom
HsOrc4. [Internet] [Thesis]. Univerzitet u Beogradu; 2018. [cited 2021 Jan 17].
Available from: https://fedorabg.bg.ac.rs/fedora/get/o:18975/bdef:Content/get.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Divac, Aleksandra 1. Promene strukture DNK izazvane proteinom
HsOrc4. [Thesis]. Univerzitet u Beogradu; 2018. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:18975/bdef:Content/get
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Southern California
18.
Slaymaker, Ian M.
Structural and biochemical studies of DNA helicase
complexes: conformational diversity of archaeal MCM.
Degree: PhD, Molecular Biology, 2014, University of Southern California
URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/363791/rec/6114
► Since their discovery nearly 30 years ago, MCM proteins have become known as the primary replicative helicase in eukaryotes and archaea; unwinding genomic double stranded…
(more)
▼ Since their discovery nearly 30 years ago, MCM
proteins have become known as the primary replicative helicase in
eukaryotes and archaea; unwinding genomic double stranded
DNA
(dsDNA). Mcm2-7 proteins are members of the AAA+ family of proteins
that harness energy from ATP hydrolysis for diverse cellular
processes. MCM proteins Mcm2, Mcm3, Mcm4, Mcm5, Mcm6 and Mcm7
(Mcm2-7) form a toroid complex that encircles
DNA as it travels
with a replication fork; initiating from origins and unwinding
dsDNA into single stranded
DNA (ssDNA) template in an ATP dependent
reaction. Polymerases then copy the ssDNA back into dsDNA, each new
copy segregates to opposing poles of the cell and cytokinesis
occurs to generate two genetically identical cells. ❧ MCM proteins
are of great interest to the medical community because
dysregulation of Mcm2-7 complexes lead to genome instability.
Furthermore, because quiescent cells are out of cell cycle, MCMs
are excellent markers for cancer. ❧ The following chapters describe
experiments using archaeal MCM homologs which expand on current
knowledge of
DNA unwinding, helicase loading, and chromatin
binding.
Advisors/Committee Members: Chen, Xiaojiang S. (Committee Chair), Forsburg, Susan (Committee Member), Bradforth, Stephen E. (Committee Member).
Subjects/Keywords: MCM; helicase; DNA topology; unwinding; structure; crystallography; DNA replication
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Slaymaker, I. M. (2014). Structural and biochemical studies of DNA helicase
complexes: conformational diversity of archaeal MCM. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/363791/rec/6114
Chicago Manual of Style (16th Edition):
Slaymaker, Ian M. “Structural and biochemical studies of DNA helicase
complexes: conformational diversity of archaeal MCM.” 2014. Doctoral Dissertation, University of Southern California. Accessed January 17, 2021.
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/363791/rec/6114.
MLA Handbook (7th Edition):
Slaymaker, Ian M. “Structural and biochemical studies of DNA helicase
complexes: conformational diversity of archaeal MCM.” 2014. Web. 17 Jan 2021.
Vancouver:
Slaymaker IM. Structural and biochemical studies of DNA helicase
complexes: conformational diversity of archaeal MCM. [Internet] [Doctoral dissertation]. University of Southern California; 2014. [cited 2021 Jan 17].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/363791/rec/6114.
Council of Science Editors:
Slaymaker IM. Structural and biochemical studies of DNA helicase
complexes: conformational diversity of archaeal MCM. [Doctoral Dissertation]. University of Southern California; 2014. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/363791/rec/6114

University of Manchester
19.
Henthorn, Nicholas.
Modelling and measurement of simple and complex DNA damage induction by ion irradiation.
Degree: PhD, 2018, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/modelling-and-measurement-of-simple-and-complex-dna-damage-induction-by-ion-irradiation(c683999f-3f6f-43f3-ae08-c3f76d867b37).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.816250
► Photons have been used in radiotherapy for a number of years, and a lot of experience has been gained; experience which does not currently exist…
(more)
▼ Photons have been used in radiotherapy for a number of years, and a lot of experience has been gained; experience which does not currently exist for protons. In order to apply this experience, and to optimise proton therapy, a dose conversion is applied, known as the Relative Biological Effectiveness (RBE). A constant RBE of 1.1 is in clinical use. However, a number of experimental studies have shown that RBE is not constant; depending on a number of factors, such as Linear Energy Transfer (LET), cell type, and dose etc. The RBE of 1.1 is based on a number of in vitro studies, however, within this data exists a significant variance. It has been estimated that proton RBE ranges from around 1, at the entrance, to around 2.5, at the distal edge. The value of 1.1 has been clinically accepted as a âsafeâ value, with no signs of significant under- or over-dosing. However, the open question of RBE, and the biologically extended range, can lead to potential degradation in treatment plan quality. For example, proton distal edges are not placed near organs at risk, where RBE is highest. A number of phenomenological models have been developed to encapsulate variable RBE. These models link cell survival parameters between photons and protons, with a scaling from LET. However, the models are fit with the same in vitro data used to derive RBE. The models also, by definition, give no information on underlying mechanisms of variable RBE, aside from implicitly stating that there is increased cell kill at increased LET. Noise in the data used to fit the models could explain the lack of clinical implementation. Mechanistically, it is believed that cell kill is a result of DNA damage and the efficacy of repair. In particular, the induction of DNA Double Strand Breaks (DSBs) has been identified as the toxic mechanism. By simulating the process of DSB induction and repair, mechanisms can be uncovered. This work presents results of such a methodology. The mechanisms that lead to direct and indirect DNA damage are simulated, with parameters of the mechanisms fit to experiments on DNA extracts or parameters taken from the literature. The mechanisms are applied to larger biological systems, making predictions of DNA damage at the cellular level. Prediction of DNA damage is correlated to conventional units that can be scored in proton therapy, dose and LET. This allows for the model predictions to be applied to clinically relevant cases, such as in treatment planning software. In all cases, the simulations predict an increase in yield, complexity, and density of DSBs with LET. This translates to an increase in misrepaired and residual DSBs, i.e. biological effect. The work provides mechanisms for the experimentally observed increase in cell kill with proton depth.
Subjects/Keywords: Radiotherapy; DNA Damage; Monte Carlo Track Structure; Geant4-DNA; Proton Therapy
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Henthorn, N. (2018). Modelling and measurement of simple and complex DNA damage induction by ion irradiation. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/modelling-and-measurement-of-simple-and-complex-dna-damage-induction-by-ion-irradiation(c683999f-3f6f-43f3-ae08-c3f76d867b37).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.816250
Chicago Manual of Style (16th Edition):
Henthorn, Nicholas. “Modelling and measurement of simple and complex DNA damage induction by ion irradiation.” 2018. Doctoral Dissertation, University of Manchester. Accessed January 17, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/modelling-and-measurement-of-simple-and-complex-dna-damage-induction-by-ion-irradiation(c683999f-3f6f-43f3-ae08-c3f76d867b37).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.816250.
MLA Handbook (7th Edition):
Henthorn, Nicholas. “Modelling and measurement of simple and complex DNA damage induction by ion irradiation.” 2018. Web. 17 Jan 2021.
Vancouver:
Henthorn N. Modelling and measurement of simple and complex DNA damage induction by ion irradiation. [Internet] [Doctoral dissertation]. University of Manchester; 2018. [cited 2021 Jan 17].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/modelling-and-measurement-of-simple-and-complex-dna-damage-induction-by-ion-irradiation(c683999f-3f6f-43f3-ae08-c3f76d867b37).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.816250.
Council of Science Editors:
Henthorn N. Modelling and measurement of simple and complex DNA damage induction by ion irradiation. [Doctoral Dissertation]. University of Manchester; 2018. Available from: https://www.research.manchester.ac.uk/portal/en/theses/modelling-and-measurement-of-simple-and-complex-dna-damage-induction-by-ion-irradiation(c683999f-3f6f-43f3-ae08-c3f76d867b37).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.816250

University of Toronto
20.
Luo, Jennifer Jing.
An Investigation into the Effect of DNA Structural Polymorphism and Single-stranded DNA Binding Proteins on Repair of Disease-associated Slipped-DNA Repeats.
Degree: 2015, University of Toronto
URL: http://hdl.handle.net/1807/69548
► Gene-specific repeat expansions are the cause of a growing list of neurological diseases, including myotonic dystrophy type 1 and Huntington's disease. The formation of slipped-DNA…
(more)
▼ Gene-specific repeat expansions are the cause of a growing list of neurological diseases, including myotonic dystrophy type 1 and Huntington's disease. The formation of slipped-DNA structures in the expanded repeat sequences is thought to drive repeat instability and pathogenesis by impairing normal DNA metabolic processes. Here I show that slipped-DNAs with nicks located within the repeat tract displayed increased structural heterogeneity relative to slipped-DNAs with nicks located in the flanking sequence. Nick-in-repeat slipped-DNAs were repaired better than nick-in-flank slipped-DNAs, likely due to increased amounts of single-stranded DNA at the nicked repeat ends allowing for better repair factor binding. Single-stranded DNA binding proteins RPA and aRPA seem to play an important part in tissue-specific instability as both complexes are overexpressed in the brains of HD patients. Neither RPA nor aRPA was required for slipped-DNA repair, although they both enhanced slipped-DNA repair efficiency.
M.Sc.
Advisors/Committee Members: Osborne, Lucy, Molecular and Medical Genetics.
Subjects/Keywords: Alternative RPA; DNA structure; Myotonic dystrophy; Replication protein A; single-stranded DNA; Slipped-DNA; 0369
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Luo, J. J. (2015). An Investigation into the Effect of DNA Structural Polymorphism and Single-stranded DNA Binding Proteins on Repair of Disease-associated Slipped-DNA Repeats. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/69548
Chicago Manual of Style (16th Edition):
Luo, Jennifer Jing. “An Investigation into the Effect of DNA Structural Polymorphism and Single-stranded DNA Binding Proteins on Repair of Disease-associated Slipped-DNA Repeats.” 2015. Masters Thesis, University of Toronto. Accessed January 17, 2021.
http://hdl.handle.net/1807/69548.
MLA Handbook (7th Edition):
Luo, Jennifer Jing. “An Investigation into the Effect of DNA Structural Polymorphism and Single-stranded DNA Binding Proteins on Repair of Disease-associated Slipped-DNA Repeats.” 2015. Web. 17 Jan 2021.
Vancouver:
Luo JJ. An Investigation into the Effect of DNA Structural Polymorphism and Single-stranded DNA Binding Proteins on Repair of Disease-associated Slipped-DNA Repeats. [Internet] [Masters thesis]. University of Toronto; 2015. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/1807/69548.
Council of Science Editors:
Luo JJ. An Investigation into the Effect of DNA Structural Polymorphism and Single-stranded DNA Binding Proteins on Repair of Disease-associated Slipped-DNA Repeats. [Masters Thesis]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/69548

University of California – Santa Cruz
21.
Jansson-Fritzberg, Linnea.
Structure and Dynamics of Telomerase.
Degree: Molecular Cell and Developmental Biology, 2018, University of California – Santa Cruz
URL: http://www.escholarship.org/uc/item/6sk3j31x
► Telomeres are repetitive, G-rich DNA sequences, along with DNA-associated proteins, that cap the ends of linear chromosomes. Telomeres serve a two-fold function; they protect the…
(more)
▼ Telomeres are repetitive, G-rich DNA sequences, along with DNA-associated proteins, that cap the ends of linear chromosomes. Telomeres serve a two-fold function; they protect the ends of chromosomes from being recognized as sites of DNA damage and they prevent fraying of chromosomes into coding regions during successive rounds of DNA replication. In proliferative cells where unregulated chromosome end shortening would be a critical problem, telomere lengths are maintained by the specialized reverse transcriptase enzyme, telomerase. Because of its requirement in proliferative cells, telomerase is also upregulated in about 90% of cancer, making it an attractive target for cancer therapeutics. Telomerase is a ribonucleoprotein, composed of a protein component, TERT, and an RNA component, TR. Telomerase reverse transcribes telomere repeats onto the 3’ end of chromosomes through its integral template within TR. Telomerase is unique among reverse transcriptases in that it is able to add multiple telomere repeats during a single binding event. The precise conformational rearrangements required for this processive telomerase action are not well understood. In this thesis, I focus on the interaction between telomerase and the nascent telomere and how reverse transcription of multiple repeats affects the actively extending telomerase complex. First, I focus on how template boundary definition ensures the faithful synthesis of the required hexameric telomere sequence and demonstrate that critical regions within both TERT and TR are responsible for establishing strict template boundary definition. Second, I focus on the interplay between DNA structure formation within the nascent telomere and the actively extending telomerase complex and show that formation of G-quadruplexes within the telomere sequence affects telomerase activity. Lastly, I discuss ongoing work using single molecule techniques to investigate dynamics of human telomerase during the telomerase catalytic cycle and the problems that must be overcome to complete this work.
Subjects/Keywords: Biochemistry; Biophysics; DNA structure; G-quadruplex; Ribonucleoprotein; RNA structure; Telomerase; telomere
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Jansson-Fritzberg, L. (2018). Structure and Dynamics of Telomerase. (Thesis). University of California – Santa Cruz. Retrieved from http://www.escholarship.org/uc/item/6sk3j31x
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Jansson-Fritzberg, Linnea. “Structure and Dynamics of Telomerase.” 2018. Thesis, University of California – Santa Cruz. Accessed January 17, 2021.
http://www.escholarship.org/uc/item/6sk3j31x.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Jansson-Fritzberg, Linnea. “Structure and Dynamics of Telomerase.” 2018. Web. 17 Jan 2021.
Vancouver:
Jansson-Fritzberg L. Structure and Dynamics of Telomerase. [Internet] [Thesis]. University of California – Santa Cruz; 2018. [cited 2021 Jan 17].
Available from: http://www.escholarship.org/uc/item/6sk3j31x.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Jansson-Fritzberg L. Structure and Dynamics of Telomerase. [Thesis]. University of California – Santa Cruz; 2018. Available from: http://www.escholarship.org/uc/item/6sk3j31x
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Northeastern University
22.
Carson, Spencer.
Regulating DNA transport through solid-state nanopores to study non-canonical DNA structures and analyze gene synthesis reactions.
Degree: PhD, Department of Physics, 2015, Northeastern University
URL: http://hdl.handle.net/2047/D20202614
► Voltage-driven transport of double-stranded DNA through nanopores holds much potential for applications in quantitative molecular biology and biotechnology, yet the microscopic details of translocation have…
(more)
▼ Voltage-driven transport of double-stranded DNA through nanopores holds much potential for applications in quantitative molecular biology and biotechnology, yet the microscopic details of translocation have proven challenging to decipher. Earlier experiments showed strong dependence of transport kinetics on pore size: fast regular transport in large pores (> 5 nm diameter), and slower yet heterogeneous transport time distributions in sub-5 nm pores, which imply a large positional uncertainty of the DNA in the pore as a function of the translocation time. In this dissertation, we show that this anomalous transport is the result of DNA self-interaction, a phenomenon which is strictly pore-diameter dependent. We identify a regime in which DNA transport is regular, producing narrow and well-behaved dwell time distributions that fit a simple drift-diffusion theory. This observation of smooth DNA translocation is then used to study the effect of epigenetic modifications on DNA transport dynamics and to analyze gene synthesis reactions. Additionally, a preliminary study is presented reporting on the detection of G-quadruplex structures using solid-state nanopores.
Subjects/Keywords: biotechnology; DNA damage; DNA mapping; epigenetics; gene synthesis; nanopore; DNA; Structure; Nucleotide sequence; Translocation (Genetics); DNA damage; Nanopores; Epigenetics; Genes; Synthesis
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Carson, S. (2015). Regulating DNA transport through solid-state nanopores to study non-canonical DNA structures and analyze gene synthesis reactions. (Doctoral Dissertation). Northeastern University. Retrieved from http://hdl.handle.net/2047/D20202614
Chicago Manual of Style (16th Edition):
Carson, Spencer. “Regulating DNA transport through solid-state nanopores to study non-canonical DNA structures and analyze gene synthesis reactions.” 2015. Doctoral Dissertation, Northeastern University. Accessed January 17, 2021.
http://hdl.handle.net/2047/D20202614.
MLA Handbook (7th Edition):
Carson, Spencer. “Regulating DNA transport through solid-state nanopores to study non-canonical DNA structures and analyze gene synthesis reactions.” 2015. Web. 17 Jan 2021.
Vancouver:
Carson S. Regulating DNA transport through solid-state nanopores to study non-canonical DNA structures and analyze gene synthesis reactions. [Internet] [Doctoral dissertation]. Northeastern University; 2015. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/2047/D20202614.
Council of Science Editors:
Carson S. Regulating DNA transport through solid-state nanopores to study non-canonical DNA structures and analyze gene synthesis reactions. [Doctoral Dissertation]. Northeastern University; 2015. Available from: http://hdl.handle.net/2047/D20202614
23.
Priscila Albuquerque de Moura.
Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte.
Degree: 2009, Universidade Federal do Rio Grande do Norte
URL: http://bdtd.bczm.ufrn.br/tedesimplificado//tde_busca/arquivo.php?codArquivo=2785
;
http://bdtd.bczm.ufrn.br/tedesimplificado//tde_busca/arquivo.php?codArquivo=2786
► Extensive studies using molecular markers on butterflies have shown how a highly fragmented landscape may result in the reduction of gene flow among patches of…
(more)
▼ Extensive studies using molecular markers on butterflies have shown how a highly fragmented landscape may result in the reduction of gene flow among patches of habitat and, consequently, increase genetic differentiation among populations. However, little is known about Heliconius geographical structure and the effects of fragmentation on the connectivity of populations. Furthermore, findings on the effects of the population structure on the dynamics of mimicry evolution in Heliconius butterflies need to be tested in H. erato and H. melpomene specimens found in other locations other than Central and northern South Americas. For the present study, we had two motivations: (1) compare the population structure of H. erato and H. melpomene given the highly fragmented Brazils Atlantic Forest habitat; and (2) studying population structure of co-mimics could give us insights into the dynamics of mimicry evolution. For this, we analysed the spatial structure and connectivity of eight populations of Heliconius butterflies, in a total of 137 H. erato specimens and 145 H. melpomene specimens, using nine microsatellites loci, 1144 AFLPs markers and 282 mitochondrial DNA sequences. In general, both species exhibited evidence of population subdivision but no isolation by distance indicating some extent of genetic differentiation among populations. Contrary to Kronforst &Gilberts (2008) Costa Rican Heliconius, H. melpomene exhibited more genetic differentiation than H. erato based on nuclear markers. However, for mitochondrial DNA, H. erato populations showed more genetic differentiation than H. melpomene. Our results corroborate to other studies on Heliconius butterflies concerning the pronounced population subdivision and local genetic drift found in this genus. Nevertheless, the pattern of this differentiation varies significantly from the pattern found in studies conducted in Central America, where H. erato is generally more differentiated and structured than H. melpomene, based on nuclear markers. This different pattern may reflect different evolutionary histories of Heliconius species in Northeastern Brazils Atlantic Forest
Estudos utilizando marcadores moleculares em borboletas têm mostrado como uma paisagem altamente fragmentada pode resultar na redução do fluxo gênico entre as manchas de habitat e, conseqüentemente, aumentar a diferenciação genética entre as populações. No entanto, pouco se sabe sobre a estrutura geográfica e os efeitos da fragmentação sobre a conectividade das populações do gênero Heliconius. Além disso, as conclusões sobre os efeitos da estrutura populacional sobre a dinâmica da evolução do mimetismo de borboletas do gênero Heliconius precisam ser testados em espécimes de H. erato e H. melpomene encontrados em outros locais, além dos da América Central norte da América do Sul. Neste estudo, tivemos duas motivações: (1) comparar a estrutura populacional de H. erato e H. melpomene dada a elevada fragmentação do Mata Atlântica Brasileira, e (2) estudar a estrutura populacional de espécies co-mímicas…
Advisors/Committee Members: Wagner Franco Molina, Márcio Zikán Cardoso, Rosane Garcia Collevatti.
Subjects/Keywords: Estrutura populacional; Heliconius; Microssatélites; AFPLs; DNA mitocondrial; ECOLOGIA; Population structure; Heliconius; Microsatellites; AFPLs; mitochondrial DNA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Moura, P. A. d. (2009). Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte. (Thesis). Universidade Federal do Rio Grande do Norte. Retrieved from http://bdtd.bczm.ufrn.br/tedesimplificado//tde_busca/arquivo.php?codArquivo=2785 ; http://bdtd.bczm.ufrn.br/tedesimplificado//tde_busca/arquivo.php?codArquivo=2786
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Moura, Priscila Albuquerque de. “Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte.” 2009. Thesis, Universidade Federal do Rio Grande do Norte. Accessed January 17, 2021.
http://bdtd.bczm.ufrn.br/tedesimplificado//tde_busca/arquivo.php?codArquivo=2785 ; http://bdtd.bczm.ufrn.br/tedesimplificado//tde_busca/arquivo.php?codArquivo=2786.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Moura, Priscila Albuquerque de. “Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte.” 2009. Web. 17 Jan 2021.
Vancouver:
Moura PAd. Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte. [Internet] [Thesis]. Universidade Federal do Rio Grande do Norte; 2009. [cited 2021 Jan 17].
Available from: http://bdtd.bczm.ufrn.br/tedesimplificado//tde_busca/arquivo.php?codArquivo=2785 ; http://bdtd.bczm.ufrn.br/tedesimplificado//tde_busca/arquivo.php?codArquivo=2786.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Moura PAd. Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte. [Thesis]. Universidade Federal do Rio Grande do Norte; 2009. Available from: http://bdtd.bczm.ufrn.br/tedesimplificado//tde_busca/arquivo.php?codArquivo=2785 ; http://bdtd.bczm.ufrn.br/tedesimplificado//tde_busca/arquivo.php?codArquivo=2786
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade do Rio Grande do Norte
24.
Moura, Priscila Albuquerque de.
Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
.
Degree: 2009, Universidade do Rio Grande do Norte
URL: http://repositorio.ufrn.br/handle/123456789/14013
► Extensive studies using molecular markers on butterflies have shown how a highly fragmented landscape may result in the reduction of gene flow among patches of…
(more)
▼ Extensive studies using molecular markers on butterflies have shown how a highly fragmented landscape may result in the reduction of gene flow among patches of habitat and, consequently, increase genetic differentiation among populations. However, little is known about Heliconius geographical
structure and the effects of fragmentation on the connectivity of populations. Furthermore, findings on the effects of the population
structure on the dynamics of mimicry evolution in Heliconius butterflies need to be tested in H. erato and H. melpomene specimens found in other locations other than Central and northern South Americas. For the present study, we had two motivations: (1) compare the population
structure of H. erato and H. melpomene given the highly fragmented Brazil s Atlantic Forest habitat; and (2) studying population
structure of co-mimics could give us insights into the dynamics of mimicry evolution. For this, we analysed the spatial
structure and connectivity of eight populations of Heliconius butterflies, in a total of 137 H. erato specimens and 145 H. melpomene specimens, using nine microsatellites loci, 1144 AFLPs markers and 282 mitochondrial
DNA sequences. In general, both species exhibited evidence of population subdivision but no isolation by distance indicating some extent of genetic differentiation among populations. Contrary to Kronforst & Gilbert s (2008) Costa Rican Heliconius, H. melpomene exhibited more genetic differentiation than H. erato based on nuclear markers. However, for mitochondrial
DNA, H. erato populations showed more genetic differentiation than H. melpomene. Our results corroborate to other studies on Heliconius butterflies concerning the pronounced population subdivision and local genetic drift found in this genus. Nevertheless, the pattern of this differentiation varies significantly from the pattern found in studies conducted in Central America, where H. erato is generally more differentiated and structured than H. melpomene, based on nuclear markers. This different pattern may reflect different evolutionary histories of Heliconius species in Northeastern Brazil s Atlantic Forest
Advisors/Committee Members: Cardoso, Márcio Zikán (advisor), CPF:83953361791 (advisor), http://lattes.cnpq.br/6310990045769627 (advisor).
Subjects/Keywords: Estrutura populacional;
Heliconius;
Microssatélites;
AFPLs;
DNA mitocondrial;
Population structure;
Heliconius;
Microsatellites;
AFPLs;
mitochondrial DNA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Moura, P. A. d. (2009). Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
. (Masters Thesis). Universidade do Rio Grande do Norte. Retrieved from http://repositorio.ufrn.br/handle/123456789/14013
Chicago Manual of Style (16th Edition):
Moura, Priscila Albuquerque de. “Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
.” 2009. Masters Thesis, Universidade do Rio Grande do Norte. Accessed January 17, 2021.
http://repositorio.ufrn.br/handle/123456789/14013.
MLA Handbook (7th Edition):
Moura, Priscila Albuquerque de. “Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
.” 2009. Web. 17 Jan 2021.
Vancouver:
Moura PAd. Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
. [Internet] [Masters thesis]. Universidade do Rio Grande do Norte; 2009. [cited 2021 Jan 17].
Available from: http://repositorio.ufrn.br/handle/123456789/14013.
Council of Science Editors:
Moura PAd. Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
. [Masters Thesis]. Universidade do Rio Grande do Norte; 2009. Available from: http://repositorio.ufrn.br/handle/123456789/14013

Tampere University
25.
Nurminen, Anssi.
A Bioinformatics Approach to Analyzing the Pathogenicity of Mutations by Using Protein Structure Information : A Study on DNA Polymerase Gamma
.
Degree: 2018, Tampere University
URL: https://trepo.tuni.fi/handle/10024/102657
► Geneettisen testauksen kustannusten laskiessa, pullonkaulaksi saatavilla olevan tiedon hyödyntämiseen on muodostumassa tietämyksemme eri geneettisten variaatioiden ja mutaatioden merkityksestä. Jokaisella henkilöllä on satoja, yksilöllisiä variaatioita perimässään…
(more)
▼ Geneettisen testauksen kustannusten laskiessa, pullonkaulaksi saatavilla olevan tiedon hyödyntämiseen on muodostumassa tietämyksemme eri geneettisten variaatioiden ja mutaatioden merkityksestä. Jokaisella henkilöllä on satoja, yksilöllisiä variaatioita perimässään joiden vaikutuksia ei tunneta. Tilanteissa joissa perinöllisen sairauden syytä pyritään selvittämään geenitutkimuksen avulla nämä variaatiot pitää pystyä tunnistamaan joko merkityksettömiksi tai merkitysellisiksi taudin kannalta, jotta oikean diagnoosin tekeminen ja sopivien hoitometelmien valinta on mahdollista.
Rakennebiologia ja bioinformatiikka tarjoavat monia keinoja mutaatioiden vaikutusten tarkasteluun. Tässä tutkimuksessa käytetään esimerkkinä DNA polymeraasi gammaa (Pol γ), joka on ainoa tunnettu entsyymi joka replikoi ja ylläpitää mitokondrionaalista DNA:ta. Pol γ tarjoaa uniikin tutkimuskohteen pistemutaatioiden vaikutuksille sen kriittisen
toiminnalisuuden ja korvaavien mekanismien puuttumisen vuoksi. Pol γ:n tunnetun proteiinirakenteen, yli 700 hengen potilasaineiston ja mutaatioiden biokemiallisen karakterisoinnin avulla pystymme tuottamaan ennennäkemättömän tarkan kuvan mutaatioiden vaikutusmekanismeista ja ennustamaan sekä tunnettujen, että vielä tuntemattomien mutaatioiden vaikutusta taudin puhkeamiseen ja etenemiseen.
Tämän tutkimuksen osana olemme kehittäneet uuden algoritmin proteiinien kolmiulotteisten rakenteiden tutkimukseen ja analysointiin, nimeltään StructureMapper. StructureMapper on skaalautuva, suurien aineistojen analysoitiin suunniteltu algoritmi, joka tarjoaa mahdollisuuksia analysoida esimerkikisi ennustusalgoritmien tulosten luotettavuutta, kokeellisen datan laatua, ja sitä voidaan hyödyntää myös mutaatioiden haitallisuuden ennustamisessa ja tutkimuksessa. Kaikkia tämän tutkimuksen osana tuotetuista menetelmistä ja työkaluista voidaan hyödyntää yleiskäyttöisesti proteiinien tutkimuksessa.; Genetic testing is becoming more and more prevalent in the field of medicine. The bottleneck in making a diagnosis based on genetic information has shifted from being able to acquire the required information by sequencing the genome of a patient, to understanding the effects of the detected, unique variations in the DNA. Mutations in the DNA can affect proteins and their structure on many levels. In a clinical setting, being able to separate the benign mutations from the pathogenic is of utmost importance.
DNA polymerase gamma (Pol γ) offers an intriguing study subject in the world of structural biology. It is the sole enzyme responsible for replicating mitochondrial DNA. Defects in its functionality can manifest with a wide variety of symptoms that are often due to single point mutations that affect its structure in a deleterious way. Through analysis of the structure of Pol γ, combined with over 700 available patient case reports and biochemical characterization of some of the mutations, we have gained an unprecedented view to the reasons behind the mutations that lead to pathogenicity and altered biological functionality of…
Subjects/Keywords: DNA polymeraasi gamma
;
POLG
;
mutaatio
;
proteiinirakenne
;
patogeenisyys
;
DNA polymerase gamma
;
mutation
;
protein structure
;
pathogenicity
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Nurminen, A. (2018). A Bioinformatics Approach to Analyzing the Pathogenicity of Mutations by Using Protein Structure Information : A Study on DNA Polymerase Gamma
. (Doctoral Dissertation). Tampere University. Retrieved from https://trepo.tuni.fi/handle/10024/102657
Chicago Manual of Style (16th Edition):
Nurminen, Anssi. “A Bioinformatics Approach to Analyzing the Pathogenicity of Mutations by Using Protein Structure Information : A Study on DNA Polymerase Gamma
.” 2018. Doctoral Dissertation, Tampere University. Accessed January 17, 2021.
https://trepo.tuni.fi/handle/10024/102657.
MLA Handbook (7th Edition):
Nurminen, Anssi. “A Bioinformatics Approach to Analyzing the Pathogenicity of Mutations by Using Protein Structure Information : A Study on DNA Polymerase Gamma
.” 2018. Web. 17 Jan 2021.
Vancouver:
Nurminen A. A Bioinformatics Approach to Analyzing the Pathogenicity of Mutations by Using Protein Structure Information : A Study on DNA Polymerase Gamma
. [Internet] [Doctoral dissertation]. Tampere University; 2018. [cited 2021 Jan 17].
Available from: https://trepo.tuni.fi/handle/10024/102657.
Council of Science Editors:
Nurminen A. A Bioinformatics Approach to Analyzing the Pathogenicity of Mutations by Using Protein Structure Information : A Study on DNA Polymerase Gamma
. [Doctoral Dissertation]. Tampere University; 2018. Available from: https://trepo.tuni.fi/handle/10024/102657
26.
Cornetta, Lucas Medeiros.
Interação entre elétrons e nucleotídeos.
Degree: Mestrado, Física, 2015, University of São Paulo
URL: http://www.teses.usp.br/teses/disponiveis/43/43134/tde-04052015-225832/
;
► Estudos teóricos e experimentais acerca de danos em biomoléculas induzidos pela captura eletrônica em meio biológico têm sido largamente discutidos ao longo da última década.…
(more)
▼ Estudos teóricos e experimentais acerca de danos em biomoléculas induzidos pela captura eletrônica em meio biológico têm sido largamente discutidos ao longo da última década. No presente trabalho, abordou-se o problema da captura eletrônica pelo nucleotídeo monofosfato 3\'-dGMP com técnicas de estrutura eletrônica, explorando estados ligados do ânion. Buscou-se investigar o ânion em fase gasosa e em solução aquosa, além de estimar barreiras de energia pontecial e energia livre associadas à sua dissociação (quebra da ligação ribose-fosfato). Utilizando os modelos de solvatação implícita (PCM) e explícita (simulação computacional com o método de Monte Carlo), concluiu-se que, em meio aquoso, o estado fundamental do ânion 3 -dGMP apresenta caráter de valência sobre a base nitrogenada (orbital com ocupação simples), em oposição ao resultado em fase gasosa, que prevê um estado ligado por dipolo. A barreira de dissociação, relativa ao estiramento da ligação entre os grupos ribose e fosfato, foi estimada em 16-30 kcal/mol, dependendo da técnica de solvatação utilizada.
Theoretical and experimental studies on the damage to biomolecules induced by electron attachment in the biological environment have been widely discussed over the past decade. In the present work, we addressed electron capture by the monophosphate nucleotide 3 -dGMP with electronic structure techniques, exploring bound anion states. We have investigated these anion states in gas phase and in aqueous solution, and estimated the potential and free energy barriers related to the dissociation reaction (breakage of the ribose-phosphate bond). Employing implicit (PCM) and explicit (computer simulation with the Monte Carlo method) solvation models, we have concluded that, in aqueous environment, the ground state of the 3-dGMP specie has valence character with the singly occupied molecular orbital localized on the base. In contrast, the gas phase results point out a dipole-bound ground state. The free energy barrier for the dissociation mechanism, according to the present results, would be around 16-30 kcal/mol in aqueous solution, depending on the salvation model.
Advisors/Committee Members: Varella, Marcio Teixeira do Nascimento.
Subjects/Keywords: Colisões; Collisions; DNA; DNA; Electronic structure; Estrutura eletrônica; Nucleotídeos; Nucleotides; Solvatação; Solvation
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cornetta, L. M. (2015). Interação entre elétrons e nucleotídeos. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/43/43134/tde-04052015-225832/ ;
Chicago Manual of Style (16th Edition):
Cornetta, Lucas Medeiros. “Interação entre elétrons e nucleotídeos.” 2015. Masters Thesis, University of São Paulo. Accessed January 17, 2021.
http://www.teses.usp.br/teses/disponiveis/43/43134/tde-04052015-225832/ ;.
MLA Handbook (7th Edition):
Cornetta, Lucas Medeiros. “Interação entre elétrons e nucleotídeos.” 2015. Web. 17 Jan 2021.
Vancouver:
Cornetta LM. Interação entre elétrons e nucleotídeos. [Internet] [Masters thesis]. University of São Paulo; 2015. [cited 2021 Jan 17].
Available from: http://www.teses.usp.br/teses/disponiveis/43/43134/tde-04052015-225832/ ;.
Council of Science Editors:
Cornetta LM. Interação entre elétrons e nucleotídeos. [Masters Thesis]. University of São Paulo; 2015. Available from: http://www.teses.usp.br/teses/disponiveis/43/43134/tde-04052015-225832/ ;

University of Oulu
27.
Pentinsaari, M. (Mikko).
Utility of DNA barcodes in identification and delimitation of beetle species, with insights into COI protein structure across the animal kingdom.
Degree: 2016, University of Oulu
URL: http://urn.fi/urn:isbn:9789526212104
► Abstract Species are the fundamental units of biological diversity, but their identification and delimitation is often difficult. The difficulties are pronounced in diverse taxa such…
(more)
▼ Abstract
Species are the fundamental units of biological diversity, but their identification and delimitation is often difficult. The difficulties are pronounced in diverse taxa such as insects. DNA barcodes, short standardized segments of the genome, have recently become a popular tool for identifying specimens to species, and are increasingly used as one of the sources of information for species delimitation. In this thesis, I studied the utility of DNA barcodes in species identification and delimitation in beetles (Coleoptera). Beetles are one of the most diverse animal groups, with nearly 400 000 known species. The Nordic beetle fauna is among the most thoroughly studied on the planet, providing excellent conditions for these studies. I also approached barcode sequences from a new angle, exploring amino acid variation and its connections to life history in a sample of the entire animal kingdom. I also studied variation and evolution at the amino acid level in large-scale samples of beetles and moths & butterflies (Lepidoptera). DNA barcodes proved to be a feasible tool for identifying species of Nordic beetles: depending on the criteria for successful identification, 95-98% of specimens could be identified to the species level based on DNA barcodes. Regardless of the delimitation method used, approximately 90% of the currently accepted species were perfectly recovered based on barcode data, and simple rules for forming consensus between delimitations improved the fit between species and barcode clusters even further. Several species that were split into two or more sequence clusters apparently include species new to science that have been previously overlooked. This conclusion is supported by preliminary morphological analysis. The study on amino acid variation revealed both a general pattern of structural conservation throughout the animal kingdom, and some interesting amino acid substitutions with potential to affect enzymatic function. Amino acid variation was more extensive in Coleoptera than in Lepidoptera, potentially due to differences in selection pressure and patterns of molecular evolution in the barcode region between the two orders.
Tiivistelmä
Laji on luonnon monimuotoisuuden perusyksikkö, mutta lajien tunnistaminen ja rajaaminen on usein vaikeaa. Vaikeudet korostuvat erityisesti hyvin monimuotoisissa eliöryhmissä kuten hyönteisissä. DNA-viivakoodit ovat lyhyitä standardoituja DNA-sekvenssejä, joiden käyttö lajien tunnistamisessa sekä yhtenä tiedon lähteenä lajien rajaamisessa on viime aikoina yleistynyt nopeasti. Tutkin väitöskirjatyössäni DNA-viivakoodien soveltuvuutta lajinmääritykseen ja lajien rajaamiseen kovakuoriaisilla. Kovakuoriaiset ovat yksi maailman lajirikkaimmista eliöryhmistä: lajeja on kuvattu lähes 400000. Pohjois-Euroopan lajisto tunnetaan koko maailman mittakaavassa poikkeuksellisen hyvin, mikä tarjoaa erinomaiset edellytykset tutkia DNA-viivakoodeihin liittyviä kysymyksiä kuoriaisilla. Tutkin DNA-viivakoodeja myös kokonaan uudesta näkökulmasta, selvittäen aminohappotason…
Advisors/Committee Members: Mutanen, M. (Marko), Kaila, L. (Lauri).
Subjects/Keywords: Coleoptera; DNA barcoding; protein structure; species delimitation; taxonomy; DNA-viivakoodit; kovakuoriaiset; lajinrajaus; proteiinirakenne; taksonomia
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Pentinsaari, M. (. (2016). Utility of DNA barcodes in identification and delimitation of beetle species, with insights into COI protein structure across the animal kingdom. (Doctoral Dissertation). University of Oulu. Retrieved from http://urn.fi/urn:isbn:9789526212104
Chicago Manual of Style (16th Edition):
Pentinsaari, M (Mikko). “Utility of DNA barcodes in identification and delimitation of beetle species, with insights into COI protein structure across the animal kingdom.” 2016. Doctoral Dissertation, University of Oulu. Accessed January 17, 2021.
http://urn.fi/urn:isbn:9789526212104.
MLA Handbook (7th Edition):
Pentinsaari, M (Mikko). “Utility of DNA barcodes in identification and delimitation of beetle species, with insights into COI protein structure across the animal kingdom.” 2016. Web. 17 Jan 2021.
Vancouver:
Pentinsaari M(. Utility of DNA barcodes in identification and delimitation of beetle species, with insights into COI protein structure across the animal kingdom. [Internet] [Doctoral dissertation]. University of Oulu; 2016. [cited 2021 Jan 17].
Available from: http://urn.fi/urn:isbn:9789526212104.
Council of Science Editors:
Pentinsaari M(. Utility of DNA barcodes in identification and delimitation of beetle species, with insights into COI protein structure across the animal kingdom. [Doctoral Dissertation]. University of Oulu; 2016. Available from: http://urn.fi/urn:isbn:9789526212104

Universidade do Rio Grande do Norte
28.
Moura, Priscila Albuquerque de.
Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
.
Degree: 2009, Universidade do Rio Grande do Norte
URL: http://repositorio.ufrn.br/handle/123456789/14013
► Extensive studies using molecular markers on butterflies have shown how a highly fragmented landscape may result in the reduction of gene flow among patches of…
(more)
▼ Extensive studies using molecular markers on butterflies have shown how a highly fragmented landscape may result in the reduction of gene flow among patches of habitat and, consequently, increase genetic differentiation among populations. However, little is known about Heliconius geographical
structure and the effects of fragmentation on the connectivity of populations. Furthermore, findings on the effects of the population
structure on the dynamics of mimicry evolution in Heliconius butterflies need to be tested in H. erato and H. melpomene specimens found in other locations other than Central and northern South Americas. For the present study, we had two motivations: (1) compare the population
structure of H. erato and H. melpomene given the highly fragmented Brazil s Atlantic Forest habitat; and (2) studying population
structure of co-mimics could give us insights into the dynamics of mimicry evolution. For this, we analysed the spatial
structure and connectivity of eight populations of Heliconius butterflies, in a total of 137 H. erato specimens and 145 H. melpomene specimens, using nine microsatellites loci, 1144 AFLPs markers and 282 mitochondrial
DNA sequences. In general, both species exhibited evidence of population subdivision but no isolation by distance indicating some extent of genetic differentiation among populations. Contrary to Kronforst & Gilbert s (2008) Costa Rican Heliconius, H. melpomene exhibited more genetic differentiation than H. erato based on nuclear markers. However, for mitochondrial
DNA, H. erato populations showed more genetic differentiation than H. melpomene. Our results corroborate to other studies on Heliconius butterflies concerning the pronounced population subdivision and local genetic drift found in this genus. Nevertheless, the pattern of this differentiation varies significantly from the pattern found in studies conducted in Central America, where H. erato is generally more differentiated and structured than H. melpomene, based on nuclear markers. This different pattern may reflect different evolutionary histories of Heliconius species in Northeastern Brazil s Atlantic Forest
Advisors/Committee Members: Cardoso, Márcio Zikán (advisor), CPF:83953361791 (advisor), http://lattes.cnpq.br/6310990045769627 (advisor).
Subjects/Keywords: Estrutura populacional;
Heliconius;
Microssatélites;
AFPLs;
DNA mitocondrial;
Population structure;
Heliconius;
Microsatellites;
AFPLs;
mitochondrial DNA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Moura, P. A. d. (2009). Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
. (Thesis). Universidade do Rio Grande do Norte. Retrieved from http://repositorio.ufrn.br/handle/123456789/14013
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Moura, Priscila Albuquerque de. “Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
.” 2009. Thesis, Universidade do Rio Grande do Norte. Accessed January 17, 2021.
http://repositorio.ufrn.br/handle/123456789/14013.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Moura, Priscila Albuquerque de. “Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
.” 2009. Web. 17 Jan 2021.
Vancouver:
Moura PAd. Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
. [Internet] [Thesis]. Universidade do Rio Grande do Norte; 2009. [cited 2021 Jan 17].
Available from: http://repositorio.ufrn.br/handle/123456789/14013.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Moura PAd. Estrutura genética populacional de Heliconius erato e Heliconius melpomene (Lepidoptera: Nymphalidae) em fragmentos de Mata Atlântica do Rio Grande do Norte
. [Thesis]. Universidade do Rio Grande do Norte; 2009. Available from: http://repositorio.ufrn.br/handle/123456789/14013
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Brno University of Technology
29.
Sečka, Martin.
Vyhledávání kvadruplexů v DNA sekvencích: Quadruplex Detection in DNA Sequences.
Degree: 2018, Brno University of Technology
URL: http://hdl.handle.net/11012/53723
► This master's thesis focuses on search for sequences potentially forming quadruplexes in DNA sequences, their visualization and filtration. For this purpose a web application was…
(more)
▼ This master's thesis focuses on search for sequences potentially forming quadruplexes in
DNA sequences, their visualization and filtration. For this purpose a web application was created in cooperation with the Institute of biophysics of Academy of science of Czech republic. This application uses a newly created algorithm able to find all possible formations of quadruplex within given input sequence. Design and implementation of this algorithm are also part of this thesis.
Advisors/Committee Members: Martínek, Tomáš (advisor), Lexa, Matej (referee).
Subjects/Keywords: DNA; sekundární struktura; kvadruplex; webová aplikace; algoritmus; DNA; secondary structure; quadruplex; web application; algorithm
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sečka, M. (2018). Vyhledávání kvadruplexů v DNA sekvencích: Quadruplex Detection in DNA Sequences. (Thesis). Brno University of Technology. Retrieved from http://hdl.handle.net/11012/53723
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sečka, Martin. “Vyhledávání kvadruplexů v DNA sekvencích: Quadruplex Detection in DNA Sequences.” 2018. Thesis, Brno University of Technology. Accessed January 17, 2021.
http://hdl.handle.net/11012/53723.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sečka, Martin. “Vyhledávání kvadruplexů v DNA sekvencích: Quadruplex Detection in DNA Sequences.” 2018. Web. 17 Jan 2021.
Vancouver:
Sečka M. Vyhledávání kvadruplexů v DNA sekvencích: Quadruplex Detection in DNA Sequences. [Internet] [Thesis]. Brno University of Technology; 2018. [cited 2021 Jan 17].
Available from: http://hdl.handle.net/11012/53723.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sečka M. Vyhledávání kvadruplexů v DNA sekvencích: Quadruplex Detection in DNA Sequences. [Thesis]. Brno University of Technology; 2018. Available from: http://hdl.handle.net/11012/53723
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Princeton University
30.
Wetzel, Joshua.
Structure-aware Approaches for Deciphering Sequence-specific Protein-DNA Interactions
.
Degree: PhD, 2019, Princeton University
URL: http://arks.princeton.edu/ark:/88435/dsp01x346d6976
► Interactions between proteins and specific genomic loci are critical to the proper functioning of all cells. The ability of a DNA-binding protein (DBP) to distinguish…
(more)
▼ Interactions between proteins and specific genomic loci are critical to the proper functioning of all cells. The ability of a
DNA-binding protein (DBP) to distinguish between its target binding sites and other genomic regions is required for a myriad of crucial functions, including transcriptional regulation, meiotic recombination, chromatin remodeling, and genome organization. However, the fundamental relationship between the amino acid sequence of a DBP and its
DNA-binding preferences remains largely elusive.
High-throughput experimental technologies for detecting protein-
DNA interactions have advanced substantially in the past decade and have enabled measurements for thousands of natural and synthetic DBP variants. However, these technologies typically require sophisticated analyses to uncover intrinsic
DNA-binding specificities from the measured signals, often have poorly understood noise and sampling profiles, and provide little insight into the underlying mechanism of interaction. Meanwhile, precise co-complex structural data provide great insight into the mechanistic principles guiding interactions between DBPs and their
DNA ligands, albeit at substantially lower throughput. These two types of data are complementary but rarely considered in concert.
In this dissertation, I describe novel computational approaches that improve the accuracy and interpretability of inferences derived from high-throughput protein-
DNA interaction data, via direct consideration of the underlying protein-
DNA structural interaction interface shared across proteins within the same
DNA-binding family. First, I describe a systematic exploration of the
DNA-binding landscape for Cys2-His2 zinc finger (C2H2-ZF) proteins, the most abundant
DNA-binding family in eukaryotes. Here we inferred the largest set of C2H2-ZF specificities to date and developed a state-of-the-art structurally-inspired method for predicting specificities for novel C2H2-ZFs. Second, I demonstrate how to leverage the large amounts of specificity data available for DBPs to develop a general framework that improves accuracy of high-throughput
DNA-binding specificity inferences by jointly considering interaction preferences for groups of proteins from the same
DNA-binding family, rewarding global consistency according to an expected similarity measure reflecting family-level structural considerations. Finally, I provide a probabilistic framework for improving interpretability of high-throughput data by mapping inferred specificities of DBPs from the same
DNA-binding family onto a common ``reference'' structural interface model derived from aggregated family-level co-complex data.
Advisors/Committee Members: Singh, Mona (advisor).
Subjects/Keywords: DNA-binding;
gene regulation;
protein-DNA interaction;
protein structure;
transcription factor;
zinc finger
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share





❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wetzel, J. (2019). Structure-aware Approaches for Deciphering Sequence-specific Protein-DNA Interactions
. (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp01x346d6976
Chicago Manual of Style (16th Edition):
Wetzel, Joshua. “Structure-aware Approaches for Deciphering Sequence-specific Protein-DNA Interactions
.” 2019. Doctoral Dissertation, Princeton University. Accessed January 17, 2021.
http://arks.princeton.edu/ark:/88435/dsp01x346d6976.
MLA Handbook (7th Edition):
Wetzel, Joshua. “Structure-aware Approaches for Deciphering Sequence-specific Protein-DNA Interactions
.” 2019. Web. 17 Jan 2021.
Vancouver:
Wetzel J. Structure-aware Approaches for Deciphering Sequence-specific Protein-DNA Interactions
. [Internet] [Doctoral dissertation]. Princeton University; 2019. [cited 2021 Jan 17].
Available from: http://arks.princeton.edu/ark:/88435/dsp01x346d6976.
Council of Science Editors:
Wetzel J. Structure-aware Approaches for Deciphering Sequence-specific Protein-DNA Interactions
. [Doctoral Dissertation]. Princeton University; 2019. Available from: http://arks.princeton.edu/ark:/88435/dsp01x346d6976
◁ [1] [2] [3] [4] [5] … [11] ▶
.