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Full-Text Articles in Life Sciences
Functional Characterization Of Cancer-Associated Dna Polymerase Ε Variants, Stephanie R. Barbari
Functional Characterization Of Cancer-Associated Dna Polymerase Ε Variants, Stephanie R. Barbari
Theses & Dissertations
Replicative DNA polymerases ε (Polε) and δ (Polδ) achieve high fidelity DNA synthesis through a precise balance of polymerization and exonucleolytic proofreading. Errors that escape proofreading are corrected by DNA mismatch repair (MMR). Ultramutated human cancers with proficient MMR carry alterations in the exonuclease domain of Polε, which were initially predicted to abolish proofreading. However, functional studies in yeast of the most recurrent Polε-P286R variant suggested defects beyond a loss of exonuclease activity. Indeed, biochemical analysis of the yeast Polε-P286R analog revealed increased polymerization capacity in addition to decreased proofreading, which enables efficient mismatch extension and bypass of replication-blocking non-B …
The Effect Of Cadmium On Ovarian Adenocarcinoma Cell Lines: An Investigation Of The Possible Mechanism Of Action, Haley Todd
Undergraduate Theses
Cadmium, a heavy metal and carcinogen, is an environmental and workplace contaminate. As a known endocrine disruptor, it can mimic the proliferative effects of estrogen and is classified as a metalloestrogen. While the proliferative effect of estrogen on cancerous cell growth has been well established, the effects of cadmium have not been fully examined. To determine if cadmium stimulates growth in two human ovarian adenocarcinoma cell lines, OVCAR3 and SKOV3, cells were treated for 48 hours with varying concentrations of cadmium, 0.001 µM – 10 µM, and growth was measured using a cell proliferation assay. Both cell lines showed a …
Biophysical Characterization Of The Par-4 Tumor Suppressor: Evidence Of Structure Outside The Coiled Coil Domain And Interactions With Platinum Chemotherapeutics, Andrea Megan Clark
Biophysical Characterization Of The Par-4 Tumor Suppressor: Evidence Of Structure Outside The Coiled Coil Domain And Interactions With Platinum Chemotherapeutics, Andrea Megan Clark
Chemistry & Biochemistry Theses & Dissertations
Prostate apoptosis response-4 (Par-4) is an apoptosis-inducing tumor suppressor protein. Full-length Par-4 has previously been shown to be a predominantly intrinsically disordered protein (IDP) under neutral conditions, with significant regular secondary structure evident only within the C-terminal coiled coil domain. However, IDPs can gain ordered structure through the process of induced folding, which often occurs under non-neutral conditions. Previous work has shown that the Par-4 leucine zipper, which is a subset of the C-terminal coiled coil domain, is disordered under neutral conditions, but forms a dimeric coiled coil at acidic pH. Increase in ionic strength was also shown to increase …
Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant
Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant
Honors Theses
Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …
Understanding The Epigenetic Role Of 8-Oxoguanine And Ogg1 In Non-Small Cell Lung Cancer, Kyrellos Ibrahim
Understanding The Epigenetic Role Of 8-Oxoguanine And Ogg1 In Non-Small Cell Lung Cancer, Kyrellos Ibrahim
CMC Senior Theses
Oxidative damage to the genome can form 8-oxoguanine (oxoG), a premutagenic lesion suggested to play an epigenetic role in the regulation of various cellular pathways. Alongside oxoG in this regulation is the 8-oxoguanine DNA glycosylase (OGG1), which primarily functions to repair oxoG damage via base excision repair, but is also implicated in recruiting NFκB and impacting gene expression associated with cancer growth. This proposal aims to build genome-wide maps of oxoG occupancy, and indirectly OGG1 localization, in healthy lung cells and in non-small cell lung cancer adenocarcinoma cells in order to identify regulatory regions in the genome at which oxoG …