Authors
Yu, LijianFaculty Advisor
Michael Volkert, Ph.D.Academic Program
Molecular Genetics and MicrobiologyUMass Chan Affiliations
Microbiology and Physiological SystemsDocument Type
Doctoral DissertationPublication Date
2011-06-29Keywords
Oxidative StressDNA Damage
DNA-Binding Proteins
Subtilisins
Proprotein Convertases
Polyadenylation
Biochemical Phenomena, Metabolism, and Nutrition
Biochemistry, Biophysics, and Structural Biology
Cells
Enzymes and Coenzymes
Genetic Phenomena
Metadata
Show full item recordAbstract
Oxidative stress is a cellular condition where cells are challenged by elevated levels of reactive oxygen species (ROS) that are produced endogenously or exogenously. ROS can damage vital cellular components, including lipid, protein, DNA and RNA. Oxidative damage to DNA often leads to cell death or mutagenesis, the underlying cause of various human disease states. Previously our laboratory discovered that human PC4 gene can prevent oxidative mutagenesis in the bacterium Escherichia coli and that the yeast homolog SUB1 has a conserved function in oxidation protection. In this thesis I examined the underlying mechanisms of PC4’s oxidation protection function. My initial efforts to examine the predicted role of SUB1 in transcription-coupled DNA repair essentially negated this hypothesis. Instead, results from our experiments suggest that PC4 and yeast SUB1 can directly protect genomic DNA from oxidative damage. While testing SUB1’s role in double strand DNA break (DSB) repair, I found the sub1Δ mutant resects DSB ends rapidly but still ligates chromosomal breaks effectively, suggesting that DSB resection is not inhibitory to nonhomologous end-joining, an important DSB repair pathway. Finally, in the course of studying transcription recovery after UV damage, I found UV induces a longer form of RPB2 mRNA and demonstrated that this is caused by alternative polyadenylation of the RPB2 mRNA and that alternative polyadenylation contributes to UV resistance. Based on results of preliminary experiments, I propose that UV activates an alternative RNA polymerase to transcribe RNA POL II mRNA, a novel mechanism to facilitate recovery from inhibition of transcription resulting from UV damage. The hypothetical polymerase switch may account for the UV-induced alternative polyadenylation of the RPB2 mRNA.DOI
10.13028/q0af-rm56Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31885Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/q0af-rm56