+publisher:"University of Illinois – Chicago" +contributor:("Nitiss, John")

University of Illinois – Chicago

1. Sun, Yilun. Molecular Pathways for Repair of Topoisomerase II-Mediated DNA Damage.

Degree: 2017, University of Illinois – Chicago

► DNA Topoisomerases play an essential role in nuclear processes such as replication and transcription by managing the topology of DNA duplexes. Topoisomerase II (Top2) is… (more)

▼ DNA Topoisomerases play an essential role in nuclear processes such as replication and transcription by managing the topology of DNA duplexes. Topoisomerase II (Top2) is a target for anti-cancer agents such as etoposide and doxorubicin, which act by trapping Top2 on DNA. This leads to accumulation of Top2-DNA covalent complexes (Top2ccs) and DNA double-strand breaks (DSBs). The mechanisms causing tumor-specific cell killing by Top2 inhibitors may arise from DNA repair defects in tumor cells. Therefore, targeting pathways that repair Top2-mediated damage is a potential strategy to enhance the action of Top2 inhibitors. We hypothesized that the primary step in repair of Top2-mediated DSBs is removal of Top2 from DNA, and that nucleolytic and proteolytic activities are required for this removal. To gain insight into the nucleolytic and proteolytic pathways, we utilized the ICE (in-vivo complex of enzyme) bioassay to detect the abortive Top2cc. With the ICE assay, we demonstrated that the nucleases Mre11 and CtIP play a critical role in repairing Top2cc in human cells. We also developed a method to detect ubiquitylation and SUMOylation of Top2cc by modifying the ICE assay. Using a yeast system, we showed that the proteasome plays a key role in degrading Top2cc. We found that depletion of ubiquitin ligase Slx5/Slx8 led to decreased ubiquitylation of Top2cc. Depletion of Siz1, a SUMO ligase, was found to reduce not only SUMOylation of Top2cc but also its ubiquitylation. These findings suggest a signaling axis wherein Siz1-mediated SUMOylation primes Top2cc for Slx5/Slx8-mediated ubiquitylation and the subsequent proteasomal degradation. We also demonstrate that RNF4, the human ortholog of Slx5/Slx8, plays an important role in repairing Top2cc by modulating its ubiquitylation and proteolysis in human cells. Remarkably, our work provides the first evidence that the proteolysis of Top2cc is negatively regulated by UBAP2L. It was found that UBAP2L binds the ubiquitylated Top2cc via UBA domain-ubiquitin hydrophobic interaction thereby sequester the ubiquitin signal to prevent the trapped protein from proteasomal destruction. Taken together, our results shed light on mechanism of action of Top2 inhibitors by elucidating DNA repair systems that may lead to identification of novel anti-cancer drug targets. Advisors/Committee Members: Nitiss, John (advisor), Beck, William (committee member), Tonetti, Debra (committee member), Mankin, Alexander (committee member), Liang, Jie (committee member), Nitiss, John (chair).

Subjects/Keywords: Topoisomerase II; etoposide; DNA repair; MRE11; the ubiquitin-proteasome pathway; RNF4; UBAP2L; cancer chemotherapy

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

APA (6^th Edition):

Sun, Y. (2017). Molecular Pathways for Repair of Topoisomerase II-Mediated DNA Damage. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/22215

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sun, Yilun. “Molecular Pathways for Repair of Topoisomerase II-Mediated DNA Damage.” 2017. Thesis, University of Illinois – Chicago. Accessed April 17, 2021. http://hdl.handle.net/10027/22215.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sun, Yilun. “Molecular Pathways for Repair of Topoisomerase II-Mediated DNA Damage.” 2017. Web. 17 Apr 2021.

Vancouver:

Sun Y. Molecular Pathways for Repair of Topoisomerase II-Mediated DNA Damage. [Internet] [Thesis]. University of Illinois – Chicago; 2017. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10027/22215.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sun Y. Molecular Pathways for Repair of Topoisomerase II-Mediated DNA Damage. [Thesis]. University of Illinois – Chicago; 2017. Available from: http://hdl.handle.net/10027/22215

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

2. Erb, Samuel. Antidepressants Accumulate in Lipid Rafts and Modify the Acylation State of G alpha S.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/20253

► Depression is a significant public health problem for which currently available medications are often ineffective while their physiological effects are routinely delayed. Previous studies from… (more)

Subjects/Keywords: Central nervous system (CNS); depression; drug action; gas chromatography‐mass spectrometry (GC‐MS) ; glial cell; heterotrimeric G protein; lipid raft; mass spectrometry (MS); membrane protein; membrane trafficking; neurochemistry; neurological disease; neuroscience; peptides; post-translational modification (PTM); protein chemistry; protein-drug interaction; protein myristoylation; protein palmitoylation; protein purification; protein translocation; proteomics; receptor; selective serotonin reuptake inhibitor (SSRI); stereoselectivity; subcellular fractionation

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APA (6^th Edition):

Erb, S. (2016). Antidepressants Accumulate in Lipid Rafts and Modify the Acylation State of G alpha S. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/20253

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Erb, Samuel. “Antidepressants Accumulate in Lipid Rafts and Modify the Acylation State of G alpha S.” 2016. Thesis, University of Illinois – Chicago. Accessed April 17, 2021. http://hdl.handle.net/10027/20253.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Erb, Samuel. “Antidepressants Accumulate in Lipid Rafts and Modify the Acylation State of G alpha S.” 2016. Web. 17 Apr 2021.

Vancouver:

Erb S. Antidepressants Accumulate in Lipid Rafts and Modify the Acylation State of G alpha S. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10027/20253.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Erb S. Antidepressants Accumulate in Lipid Rafts and Modify the Acylation State of G alpha S. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/20253

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

3. Xie, Jia. Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/20256

► High-grade serous carcinoma (HGSC) is the most common and lethal histotype of ovarian cancer. Radiation is usually used as a second-line treatment against the disease.… (more)

▼ High-grade serous carcinoma (HGSC) is the most common and lethal histotype of ovarian cancer. Radiation is usually used as a second-line treatment against the disease. In spite of numerous clinical studies indicating efficacy of radiation therapy in patients suffering from disease recurrence, it is seldom used clinically due to severe dose-related toxicity. Discovery and utilization of novel radiosensitizers could control the toxicity and enable effective therapeutic application of radiation. Fractalkine receptor (CX3CR1) belongs to a chemokine family of G protein-coupled receptors. Our previous publications showed that CX3CR1 is not expressed in normal ovarian surface epithelium and is expressed in primary and metastatic epithelial ovarian carcinoma. Moreover, transient downregulation of CX3CR1 in ovarian cancer cells will impair their proliferation as well as their migration and adhesion to peritoneal mesothelial cells. Therefore, we proposed combining CX3CR1 downregulation and radiation as a strategy for reducing the dose of radiation while maintaining the therapeutic efficacy. The experimental observations indicated that transient downregulation of CX3CR1 in most HGSC cell lines can lead to radiosensitization, as determined by clonogenic assay. However, loss of CX3CR1 does not affect radiosensitivity in ovarian cancer cells that express wild-type p53. There are several altered characteristics that may contribute to resistance to ionizing radiation, including enhanced DNA damage repair, and adaptive response to the radiation-induced ROS (Reactive Oxygen Species). Specifically, my results indicated that downregulation of CX3CR1 can abrogate the phosphorylation and activation of DNA double-strand break repair related proteins following ionizing radiation. The unrepaired DNA damage leads to damage persistence and ultimately contributes to radiosensitization. Another mechanism by which CX3CR1 knockdown alters radiosensitivity is the regulation of cellular redox capacity, where loss of CX3CR1 leads to elevated ROS levels. Taken together, my study demonstrated for the novel findings that loss of CX3CR1 can sensitize HGSC cells to ionizing radiation through the regulation of DNA damage response and intracellular redox status. Advisors/Committee Members: Barbolina, Maria (advisor), Nitiss, John (committee member), Jeong, Hyun-Young (committee member), Burdette, Joanna (committee member), Diamond, Alan (committee member).

Subjects/Keywords: high-grade serous ovarian cancer; ionizing radiation; fractalkine receptor; DNA damage repair; reactive oxygen species

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

APA (6^th Edition):

Xie, J. (2016). Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/20256

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Xie, Jia. “Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells.” 2016. Thesis, University of Illinois – Chicago. Accessed April 17, 2021. http://hdl.handle.net/10027/20256.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Xie, Jia. “Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells.” 2016. Web. 17 Apr 2021.

Vancouver:

Xie J. Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10027/20256.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Xie J. Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/20256

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

4. Gursoy, Gamze. Three-Dimensional Chromosome Organization in Eukaryotes: Novel Computational Approaches.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/21633

► DNA is the carrier of genetic information and is passed down from one generation to the next. With the completion of Human Genome Project, this… (more)

▼ DNA is the carrier of genetic information and is passed down from one generation to the next. With the completion of Human Genome Project, this genetic information is more accessible than ever before. Cells from different tissues carry the same genetic alphabet, but they exhibit different properties and perform different functions depending on the regulation of gene expression. We now know that the spatial organization of the genome occupies an important role in the regulation of gene expression as well as the repair, recombination and replication of DNA because of the information provided by recent experimental techniques based on fluorescence in-situ hybridization (FISH) and chromosome conformation capture (3C). However, understanding detailed mechanisms important for cellular activities from existing experimental data requires computational modeling of the 3D structures of chromatin. Here we describe a computational pipeline for constructing ensembles of chromatin chains from diverse experimental data. We have developed novel sampling tools to build spatial structures of chromosomes in an eﬀort to understand the fundamental gene regulation mechanisms involving the eﬀect of nuclear space in maintaining the epigenetic state of the cell, the physical factors and mechanisms that determine the genome organization, and long-distance chromatin interactions that promote cell-speciﬁc gene expression. We first studied the effect of nuclear confinement on the folding landscape of human chromosomes. We developed a geometrical algorithm based on the Importance Sampling technique to generate ensembles of three-dimensional chromosome chains in the severe conﬁnement of the cell nucleus. Our model, named Constrained Self-Avoiding Chromatin (C-SAC), showed how experimentally observed scaling properties of human chromosome folding, the formation of higher-order structural units such as Topologically Associated Domains (TADs), and the intrinsic propensity to form long-range chromatin loops emerge from the conﬁnement of the cell nucleus. Our ﬁndings further highlight the importance of nuclear size as a potential regulator of epigenetic programming of cells. The detailed understanding of diﬀerent cellular states in mammalian cell diﬀerentiation require comprehensive analysis of the interactions in the whole genome. Thus, we next studied the origin of the chromatin interaction patterns of budding yeast genome observed by genome-wide 3C studies. With further improvement of multi-chromosome Constrained Self-Avoiding Chromatin (mC-SAC) model, we generated ensembles of model budding yeast genomes using nuclear landmarks observed with imaging techniques as constraints. Comparison of ensembles of folded chromosomes from mC-SAC model with those from genome-wide 3C studies shows that the majority of measured interactions are well captured (at an accuracy of 90%). We showed that nuclear confinement dictates the formation of intra-chromosomal interactions, while centromere tethering dictates the formation of inter-chromosomal interactions.… Advisors/Committee Members: Liang, Jie (advisor), Dai, Yang (committee member), Ma, Ao (committee member), Nitiss, John L (committee member), Merrill, Bradley (committee member), Liang, Jie (chair).

Subjects/Keywords: three-dimensional structures of chromosomes; sequential importance sampling; chromosome conformation capture

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

APA (6^th Edition):

Gursoy, G. (2016). Three-Dimensional Chromosome Organization in Eukaryotes: Novel Computational Approaches. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/21633

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gursoy, Gamze. “Three-Dimensional Chromosome Organization in Eukaryotes: Novel Computational Approaches.” 2016. Thesis, University of Illinois – Chicago. Accessed April 17, 2021. http://hdl.handle.net/10027/21633.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gursoy, Gamze. “Three-Dimensional Chromosome Organization in Eukaryotes: Novel Computational Approaches.” 2016. Web. 17 Apr 2021.

Vancouver:

Gursoy G. Three-Dimensional Chromosome Organization in Eukaryotes: Novel Computational Approaches. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10027/21633.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gursoy G. Three-Dimensional Chromosome Organization in Eukaryotes: Novel Computational Approaches. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/21633

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

5. Li, Jing. Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ).

Degree: 2017, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/22078

► The repair of DNA double-strand breaks (DSB) is central to the maintenance of genomic integrity. Major DSB repair pathways in mammalian cells include homologous recombination… (more)

▼ The repair of DNA double-strand breaks (DSB) is central to the maintenance of genomic integrity. Major DSB repair pathways in mammalian cells include homologous recombination and non-homologous end joining (NHEJ). NHEJ is a template-independent mechanism, yet many NHEJ repair products carry limited genetic changes, which suggest that NHEJ includes mechanisms to minimize error. In yeast, mutations of tyrosyl-DNA phosphodiesterase 1 (TDP1) reduced NHEJ fidelity. We are investigating the role of TDP1 in NHEJ in human cells. Using affinity capture chromatography, we found human TDP1 physically interacted with the required NHEJ protein -XLF. This interaction also stimulated DNA binding for both TDP1 and XLF, and formation of TDP1:XLF:DNA complexes. TDP1 can remove adducts from DNA 3’ ends, and TDP1:XLF interactions stimulated this activity on double-stranded, but not on single-stranded DNA. To investigate role of TDP1 in NHEJ in human cells, we used CRISPR/Cas9-mediated genome editing to generate TDP1-knockout HEK 293 cells, which showed an expected increase sensitivity to Topoisomerase 1 poisoning and ionizing radiation. Using a chromosomally- integrated end-joining reporter substrate, we observed an average 4-fold reduction in repair of I-SceI-induced DSBs in TDP1-KO cells as compared to wild type cells. These data indicate that, in human cells, TDP1 contributes to repair of DSBs that lack 3’ end damage. NextGen sequencing of end-joining junctions generated in this reporter system showed that TDP1 deficiency resulted in increased use of microhomology in joining. Within the N-terminal domain of TDP1, phosphorylation at serine 81 (S81) has been reported to regulate interaction with DNA repair factors, including DNA ligase III, XRCC4 and PARP1. We observed that the TDP1-S81 phosphomimetic, TDP1-S81E, had 10-fold reduced XLF binding, and ectopic expression of TDP1-S81E in TDP1-knockout cells failed to restore NHEJ activity. These data suggest that phosphorylation of TDP1-S81 regulates TDP1 participation in NHEJ, and may also direct TDP1 towards DNA ligase III-related pathways. Our observations support the hypothesis that TDP1 participates in mammalian NHEJ, and contribute important details to our understanding of DNA repair. Advisors/Committee Members: Hanakahi, Les (advisor), Nitiss, John (committee member), Mankin, Alexander (committee member), Burdette, Joanna (committee member), Thomas, Douglas (committee member), Hanakahi, Les (chair).

Subjects/Keywords: tyrosyl-DNA phosphodiesterase 1 (TDP1); non-homologous end joining (NHEJ); DNA double-strand breaks (DSB)

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

APA (6^th Edition):

Li, J. (2017). Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ). (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/22078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Li, Jing. “Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ).” 2017. Thesis, University of Illinois – Chicago. Accessed April 17, 2021. http://hdl.handle.net/10027/22078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Li, Jing. “Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ).” 2017. Web. 17 Apr 2021.

Vancouver:

Li J. Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ). [Internet] [Thesis]. University of Illinois – Chicago; 2017. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10027/22078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Li J. Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ). [Thesis]. University of Illinois – Chicago; 2017. Available from: http://hdl.handle.net/10027/22078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

6. Summerlin, Matthew Brock. Small Molecule And Protein Modifiers of The NHEJ Pathway.

Degree: 2018, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/23046

► Non-Homologous End Joining (NHEJ) is a pathway for the repair of DNA doube-strand breaks (DSBs) that is active throughout the cell cycle and does not… (more)

▼ Non-Homologous End Joining (NHEJ) is a pathway for the repair of DNA doube-strand breaks (DSBs) that is active throughout the cell cycle and does not use a template to direct the repair. NHEJ is dependent upon the Ku70/80, DNA-PKcs,XRCC4, Ligase IV, and XLF proteins, and deficiency in any one of these factors results in failure of DSB repair by NHEJ. Additionally, proteins and small molecules have been shown to contribute to NHEJ. Deficiencies in these so-called “accessory” factors generally results in reduced NHEJ efficiency, rather than loss of NHEJ function. This dissertation examines the roles of two types of NHEJ accessory molecules, and the work presented here represents two studies. The first study focused on the small molecule myo-inositol hexakisphosphate (IP6), which has previously been shown to contribute to NHEJ in vitro. A biotinylated version of IP6 (IP6-bio) was developed and characterized as a possible tool to study the role of IP6 in NHEJ and other cellular processes. IP6-bio was similar to native IP6 in its ability to contribute to NHEJ in vitro and interacted with the required NHEJ factor Ku70/80, which had previously been reported to bind IP6. IP6-bio was not bound by other NHEJ factors. We concluded from the se data that IP6-bio can be used as a tool to study the role of IP6 in NHEJ. IP6-bio was also shown to interact with the known IP6-binding protein casein kinase 2 (CK2). Binding of IP6-bio by established IP6-binding proteins Ku70/80 and CK2 indicated that the critical determinants for IP6—binding were present in IP6-bio, and suggested that IP6-bio might be used to identify new IP6-binding proteins. Competition experiments using IP6 and less phosphorylated inositol phosphates as competitors showed that IP6-bio-binding proteins were preferentially competed off by IP6 and not by other inositol phosphates. These data indicate that proteins that bound IP6-bio may be bona fide IP6-binding proteins. Along these lines, one protein from the HEK293 extract that bound IP6-bio was the nucleolar protein nucleolin, which has been shown to participate in chromatin remodeling to facilitate DSB repair. Taken together the results of this study demonstrate that IP6-bio can by synthesized and used as a tool to investigate the role of IP6 in cellular processes, and to identify new IP6-binding proteins. The second study investigated the role of the small proteins encoded by the Cell Cycle Regulator of NHEJ (CYREN) gene in NHEJ. CYREN-deficient cells had reduced end-joining and increased sensitivity to agents that cause DNA damage that requires NHEJ for repair. Additionally, extracts prepared from CYREN-deficient cells had reduced NHEJ activity in vitro. CYREN-encoded proteins were found to physically interact with the required NHEJ protein XLF. Further, CYREN-XLF interaction impacted DNA-binding by XLF, and reduced XLF-XRCC4-DNA interactions. We interpret these data as a role for CYREN in regulating the number of DNA ends that are processed during NHEJ to minimize error. Overall, this study identifies… Advisors/Committee Members: Hanakahi, Leslyn (advisor), Nitiss, John (committee member), Burdette, Joanna (committee member), Thomas, Doug (committee member), Mankin, Alexander (committee member), Hanakahi, Leslyn (chair).

Subjects/Keywords: NHEJ IP6 CYREN

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

APA (6^th Edition):

Summerlin, M. B. (2018). Small Molecule And Protein Modifiers of The NHEJ Pathway. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/23046

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Summerlin, Matthew Brock. “Small Molecule And Protein Modifiers of The NHEJ Pathway.” 2018. Thesis, University of Illinois – Chicago. Accessed April 17, 2021. http://hdl.handle.net/10027/23046.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Summerlin, Matthew Brock. “Small Molecule And Protein Modifiers of The NHEJ Pathway.” 2018. Web. 17 Apr 2021.

Vancouver:

Summerlin MB. Small Molecule And Protein Modifiers of The NHEJ Pathway. [Internet] [Thesis]. University of Illinois – Chicago; 2018. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10027/23046.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Summerlin MB. Small Molecule And Protein Modifiers of The NHEJ Pathway. [Thesis]. University of Illinois – Chicago; 2018. Available from: http://hdl.handle.net/10027/23046

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

7. Chen, Cheng-Fen. Functional Study of the Regulation of DNA Topoisomerase II and its Cellular Role in Drug Responsiveness.

Degree: 2012, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/8139

► Resistance to chemotherapeutic agents often occurs in many cancers and is a barrier to effective treatment. Such resistance is multifactoral and one is associated with… (more)

▼ Resistance to chemotherapeutic agents often occurs in many cancers and is a barrier to effective treatment. Such resistance is multifactoral and one is associated with the altered expression of drug’s target. DNA topoisomerase II (Top2) is an essential cellular enzyme involved in DNA metabolism and the target of important chemotherapeutic agents. In mammalian cells, there are two isoforms of DNA topoisomease II, designated Top2a and Top2b. We first determined the role of Top2a in Top2 poison-mediated responsiveness. A reduced expression of Top2a resulted in drug-resistance in cancer cells. Our previous work suggested that the transcription factor NF-YB is a negative regulator of Top2a, working through the Top2a promoter (Morgan and Beck, Mol.Pharmacol 59:203,2001). Our data suggest that the increased NF-YB may be related to or be the cause of reduced Top2a in drug-resistant cells. Furthermore, recent studies indicate that microRNAs are often aberrantly expressed in cancer and may mediate drug responsiveness. MicroRNAs function through base pairing with protein coding mRNA 3’-untranslated regions (3’-UTRs) for mRNA degradation or translational repression. We have found by microRNA profiling that one microRNA, hsa-miR-485-3p, is consistently expressed at substantially lower levels in drug resistant CEM/VM-1-5 cells and microRNA target-predicting algorithms revealed that hsa-miR-485-3p has a potential target to 3’-UTR of NF-YB. We further validated the binding of hsa-miR-485-3p to 3’-UTR of NF-YB. Moreover, ectopic expression of hsa-miR-485-3p repressed NF-YB expression and rescued the expression of Top2a. On the other hand, we constructed tetracycline inducible system to turn-on and -off the expression of Top2a shRNA with and without the adding of antibiotic doxycycline (Doxy), respectively. However, we observed the cytotoxicity effect of doxycycline in CEM cells and all other cancer cell lines tested. The inhibitory effect of doxycycline on cancer cell lines was partly due to apoptosis of the cancer cells. Furthermore, we observed the downregulation of Top2a and upregulation of Top2b in Doxy-treated cells. Our results presented herein suggest that the upregulation of Top2b in Doxy-treated cells is not mediated by differentiation of the cells. Advisors/Committee Members: Beck, William T. (advisor), Tonetti, Debra (committee member), Nitiss, John L. (committee member), Wang, Zaijie Jim (committee member), He, Xiaolong (committee member), Mo, Yin-Yuan (committee member).

Subjects/Keywords: Topoisomerase; NF-YB; MicroRNA; Drug Resistance; Nuclear factor-YB

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

APA (6^th Edition):

Chen, C. (2012). Functional Study of the Regulation of DNA Topoisomerase II and its Cellular Role in Drug Responsiveness. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/8139

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chen, Cheng-Fen. “Functional Study of the Regulation of DNA Topoisomerase II and its Cellular Role in Drug Responsiveness.” 2012. Thesis, University of Illinois – Chicago. Accessed April 17, 2021. http://hdl.handle.net/10027/8139.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chen, Cheng-Fen. “Functional Study of the Regulation of DNA Topoisomerase II and its Cellular Role in Drug Responsiveness.” 2012. Web. 17 Apr 2021.

Vancouver:

Chen C. Functional Study of the Regulation of DNA Topoisomerase II and its Cellular Role in Drug Responsiveness. [Internet] [Thesis]. University of Illinois – Chicago; 2012. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10027/8139.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chen C. Functional Study of the Regulation of DNA Topoisomerase II and its Cellular Role in Drug Responsiveness. [Thesis]. University of Illinois – Chicago; 2012. Available from: http://hdl.handle.net/10027/8139

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

8. Suarez Del Pino, Jose Antonio. Development of Polymeric-Drug Conjugates for Delivering the HSP90 Inhibitor SNX5422.

Degree: 2017, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/22198

► Heat shock protein 90 (HSP90) inhibition has been considered as a potential treatment option for prostate cancer. However, several HSP90 inhibitors including SNX5422 were removed… (more)

▼ Heat shock protein 90 (HSP90) inhibition has been considered as a potential treatment option for prostate cancer. However, several HSP90 inhibitors including SNX5422 were removed from cancer clinical trials due to visual toxicities. Recent animal studies showed retinal damage produced by HSP90 inhibitors and suggested a relationship between the plasma/eye ratio of the inhibitor and the retinal damage produced. The blood ocular barrier is known to be an obstacle for large molecules like polymers. Therefore, a polymer-HSP90 inhibitor conjugate could restrict the access to the eye of the inhibitor achieving a higher plasma/eye ratio than the free HSP90 inhibitor. The purpose of this study was to develop a PEG-SNX5422 conjugate through a dendritic structure (EDTA) to allow the incorporation up to 3 SNX5422 molecules per PEG chain. The system includes Cathepsin B degradable linkers for enzymatically triggered release of the drug. We synthesized several PEG-SNX5422 conjugates with different PEG lengths (5k to 20k) and different number of SNX5422 molecules attached to the polymer chain. The conjugates where submitted to an optimization process testing their in vitro characteristics: all the conjugates were stable in different buffers, including serum proteins, and able to release SNX5422 in the presence of the enzyme Cathepsin B. We observed a relationship between water solubility and growth inhibition properties of the conjugates against 2 different prostate cancer cell lines. PEG20k conjugates had the highest stability, water solubility and cytotoxic activity against prostate cancer cells, therefore it was selected for in vivo testing using a mouse model. PEG20k-SNX3 conjugates showed a significantly higher plasma/eye ratio than the free drug, suggesting that these conjugates can modify the biodistribution of SNX5422 and reduce its visual toxicities. Advisors/Committee Members: Kolhatkar, Rohit (advisor), Desai, Surbhi (committee member), Nitiss, John L (committee member), Gemeinhart, Richard A (committee member), Hong, Seungpyo (committee member), Kolhatkar, Rohit (chair).

Subjects/Keywords: HSP90; SNX5422; Polymer-Drug Conjugates; PEG; prostate cancer

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APA (6^th Edition):

Suarez Del Pino, J. A. (2017). Development of Polymeric-Drug Conjugates for Delivering the HSP90 Inhibitor SNX5422. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/22198

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Suarez Del Pino, Jose Antonio. “Development of Polymeric-Drug Conjugates for Delivering the HSP90 Inhibitor SNX5422.” 2017. Thesis, University of Illinois – Chicago. Accessed April 17, 2021. http://hdl.handle.net/10027/22198.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Suarez Del Pino, Jose Antonio. “Development of Polymeric-Drug Conjugates for Delivering the HSP90 Inhibitor SNX5422.” 2017. Web. 17 Apr 2021.

Vancouver:

Suarez Del Pino JA. Development of Polymeric-Drug Conjugates for Delivering the HSP90 Inhibitor SNX5422. [Internet] [Thesis]. University of Illinois – Chicago; 2017. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10027/22198.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Suarez Del Pino JA. Development of Polymeric-Drug Conjugates for Delivering the HSP90 Inhibitor SNX5422. [Thesis]. University of Illinois – Chicago; 2017. Available from: http://hdl.handle.net/10027/22198

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Open Access Theses and Dissertations