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Address: 4-734 BSB
Phone: (319) 335-7501
Mentor: M. Todd Washington, PhD
Undergraduate Institution: Winona State University, Winona, MN, BS
Year Entered Into Program: 2012
The human genome is constantly subjected to environmental and genetic stressors that lead to DNA damage and mutations. DNA damage blocks normal replication; this block is overcome through the use of translesion synthesis (TLS). Special TLS polymerases are recruited to stalled replication forks caused by DNA damage. These TLS polymerases, including pol η, pol κ, pol ι, and Rev1, are able to accommodate the DNA damage within their active site but are known to be low-fidelity and effect numerous mutations. Although much research has been done to understand the structures and mechanisms of the TLS polymerases, very little work has been conducted to understand their regulation. The way in which these polymerases are recruited to proliferating cell nuclear antigen (PCNA) that has been ubiquitin-modified (UbPCNA) in response to DNA damage at the stalled DNA replication fork is of key importance in beginning to understand the regulation of macromolecular complexes. I proposed to conduct a detailed study of the recruitment of TLS polymerases to both PCNA and UbPCNA and formation of the resulting macromolecular complexes. A more thorough understanding of this recruitment will allow targeting of these error-prone polymerases with small-molecule inhibitors in order to reduce genome mutations.
Pryor, JM, Dieckman, LM, Boehm, EM, and Washington MT.: Eukaryotic Y-Family Polymerases: A Biochemical and Structural Perspective. Nucl Acids Mol Biol (Springer Book) (In Press)
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