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You searched for +publisher:"Vanderbilt University" +contributor:("Dr. Melanie Ohi"). Showing records 1 – 3 of 3 total matches.

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Vanderbilt University

1. McCann, Tyler Scott. Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1.

Degree: PhD, Cell and Developmental Biology, 2016, Vanderbilt University

Proper regulation of gene transcription is an essential process for any cell. Failure to precisely control the procedure of transcription can lead to developmental defects, disease, and even death. Within the last 20 years, ubiquitin, and other factors of the ubiquitin proteasome system have been shown to be extensively involved in the control of various steps of transcription. The Saccharomyces cerevisiae protein Asr1, is the defining member of an evolutionarily conserved set of proteins that contain a RING finger, a PHD finger, and a domain that binds the C-terminal repeat region of RNA polymerase II (RNAPII) called the RPC protein family. Asr1 is recruited to RNAPII in response to hyperphosphorylation of its regulatory C-terminal tail. Once bound, Asr1 oligoubiquitylates at least two subunits of RNAPII, leading to the ejection of the dissociable heterodimer Rpb4 and Rpb7, as well as the transcriptional inactivation of the polymerase complex. Despite the clear biochemical effects Asr1 has on RNAPII, a biological role for Asr1 within the cell has remained elusive. Within this dissertation, I present evidence that Asr1 is involved in the silencing of transcription of genes located at subtelomeric regions. Asr1 has been observed to associate with subtelomeric chromatin, and disruption of the ability of Asr1 to ubiquitylate RNAPII induces transcription at these regions. Asr1 also physically associates with Ubp3, a ubiquitin specific protease with a known role in the regulation of silent chromatin at sub-telomeric regions. I show that Asr1 and Ubp3 have antagonistic roles in both the ubiquitylation of RNAPII as well as the transcription of genes located in telomere proximal regions. The evidence presented in this dissertation reveal the importance of non-proteolytic ubiquitylation in the control of transcription, but also sheds light on a poorly understood family of eukaryotic ubiquitin-ligases. Advisors/Committee Members: Dr. Todd Graham (committee member), Dr. Melanie Ohi (committee member), Dr. Tony Weil (committee member), Dr. Stephen Hann (Committee Chair).

Subjects/Keywords: ubiquitin; silencing; RNA polymerase II; transcription; chromatin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

McCann, T. S. (2016). Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10415

Chicago Manual of Style (16th Edition):

McCann, Tyler Scott. “Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed September 26, 2020. http://hdl.handle.net/1803/10415.

MLA Handbook (7th Edition):

McCann, Tyler Scott. “Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1.” 2016. Web. 26 Sep 2020.

Vancouver:

McCann TS. Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2020 Sep 26]. Available from: http://hdl.handle.net/1803/10415.

Council of Science Editors:

McCann TS. Elucidation of the Biological Function of the RPC Family Ubiquitin Ligase Asr1. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/10415


Vanderbilt University

2. Pyburn, Tasia Marie. Structural Analysis of the Helicobacter pylori Toxin VacA.

Degree: PhD, Cell and Developmental Biology, 2017, Vanderbilt University

CELL AND DEVELOPMENTAL BIOLOGY Structural Analysis of the Helicobacter pylori toxin VacA Tasia Marie Pyburn Dissertation under the direction of Associate Professor Melanie Ohi Helicobacter pylori is a Gram-negative bacterium that colonizes the human stomach and contributes to peptic ulceration and gastric adenocarcinoma. One of the most important H. pylori virulence determinants is a secreted pore-forming toxin known as vacuolating cytotoxin A (VacA). Secreted as an 88 kDa protein, VacA is composed of an N-terminal p33 domain and a C-terminal p55 domain which assemble into multiple types of water-soluble oligomers including hexamers, heptamer, dodecamers, and tetradecamers. We have determined three-dimensional (3D) structures of VacA s1/i1/m1 oligomeric conformations at ~15 Å resolution as well as three mutant forms of VacA. At this resolution, differences between the mutants and VacA s1/i1/m1 could not be discerned. Therefore, cryo-EM has been performed on VacA s1/i1/m1 and a structure has been determined of a VacA dodecamer to the highest resolution to date, ~10Å resolution. The structural organization of membrane-bound VacA has not been characterized in any detail and the role(s) of specific VacA domains in membrane binding and insertion are unclear. Our goal is to understand how VacA transitions from a soluble protein to a membrane inserted protein and how it organizes on membrane. Using a combination of in vitro liposome binding, biochemical assays, and single particle electron microscopy (EM), we show membrane-bound VacA organizes into hexameric oligomers. Comparison of the two-dimensional averages of membrane-bound and soluble VacA hexamers generated using single particle EM reveals structural differences within the central pore-forming region of the oligomers indicating that membrane interactions induce a structural change within the p33 domain. Analyses of VacA variants demonstrate that while the p55 domain can bind membranes, the p33 domain is required for membrane insertion. Surprisingly, neither VacA oligomerization nor the presence of putative transmembrane GXXXG repeats in the p33 domain is required for membrane insertion. These findings provide new insights into the process by which VacA binds and inserts into the lipid bilayer to form membrane channels. Approved _______________________________________________ Date __________________ Melanie D. Ohi, Ph.D. Advisors/Committee Members: Dr. Melanie Ohi (committee member), Dr. Ethan Lee (committee member), Dr. Matthew Tyska (committee member), Dr. Timothy Cover (committee member), Dr. James Goldenring (Committee Chair).

Subjects/Keywords: structure; cryo-EM; negative stain EM; Helicobacter pylori; VacA

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Pyburn, T. M. (2017). Structural Analysis of the Helicobacter pylori Toxin VacA. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10845

Chicago Manual of Style (16th Edition):

Pyburn, Tasia Marie. “Structural Analysis of the Helicobacter pylori Toxin VacA.” 2017. Doctoral Dissertation, Vanderbilt University. Accessed September 26, 2020. http://hdl.handle.net/1803/10845.

MLA Handbook (7th Edition):

Pyburn, Tasia Marie. “Structural Analysis of the Helicobacter pylori Toxin VacA.” 2017. Web. 26 Sep 2020.

Vancouver:

Pyburn TM. Structural Analysis of the Helicobacter pylori Toxin VacA. [Internet] [Doctoral dissertation]. Vanderbilt University; 2017. [cited 2020 Sep 26]. Available from: http://hdl.handle.net/1803/10845.

Council of Science Editors:

Pyburn TM. Structural Analysis of the Helicobacter pylori Toxin VacA. [Doctoral Dissertation]. Vanderbilt University; 2017. Available from: http://hdl.handle.net/1803/10845


Vanderbilt University

3. Burns, Laura Titus. Nuclear Structure in Budding yeast: Impacts of Chromatin Organization and Gene Expression.

Degree: PhD, Cell and Developmental Biology, 2013, Vanderbilt University

The genome of a eukaryotic cell tightly packed within the nucleus with a high degree of structural organization. Two mechanisms accounting for nuclear structure and the dynamics of subnucler organization in S. cerevisiae are presented within. First, two powerful genetic screens identify requirements for the RSC chromatin-remodeling complex in maintaining nuclear morphology. The major NE-malformations observed in rsc mutants likely result from aberrant transcription and lipid homeostasis. Second, nuclear organization of transcriptional events in response to osmotic stress in S. cerevisiae involves the relocalization of the Hot1 transcription factor to foci that overlap with corresponding target genes. Casein Kinase II negatively regulates Hot1 localization to foci, and also leads to a reduced transcriptional response. These results suggest that the nuclear organization of transcription events impact the stochastic activity of environmentally induced genes. In conclusion, both chromatin organization and transcription events result in dynamic alterations in nuclear structure impacting the output of the genome. Advisors/Committee Members: Dr. P. Anthony Weil (committee member), Dr. Melanie Ohi (committee member), Dr. Todd Graham (committee member), Dr. Susan Wente (committee member), Dr. William Tansey (Committee Chair).

Subjects/Keywords: nuclear structure; transcription; chromatin remodeling; MAP kinase signalling

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Burns, L. T. (2013). Nuclear Structure in Budding yeast: Impacts of Chromatin Organization and Gene Expression. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14815

Chicago Manual of Style (16th Edition):

Burns, Laura Titus. “Nuclear Structure in Budding yeast: Impacts of Chromatin Organization and Gene Expression.” 2013. Doctoral Dissertation, Vanderbilt University. Accessed September 26, 2020. http://hdl.handle.net/1803/14815.

MLA Handbook (7th Edition):

Burns, Laura Titus. “Nuclear Structure in Budding yeast: Impacts of Chromatin Organization and Gene Expression.” 2013. Web. 26 Sep 2020.

Vancouver:

Burns LT. Nuclear Structure in Budding yeast: Impacts of Chromatin Organization and Gene Expression. [Internet] [Doctoral dissertation]. Vanderbilt University; 2013. [cited 2020 Sep 26]. Available from: http://hdl.handle.net/1803/14815.

Council of Science Editors:

Burns LT. Nuclear Structure in Budding yeast: Impacts of Chromatin Organization and Gene Expression. [Doctoral Dissertation]. Vanderbilt University; 2013. Available from: http://hdl.handle.net/1803/14815

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