Structural and Biochemical Analysis of Translesion Synthesis DNA Polymerases

Document Type

Grant Proposal

Date Accepted

Spring 2010

Project Description/Abstract

The integrity of DNA is essential for the survival of all living organisms. However, cellular DNA is under constant attack by a variety of internal and external sources. Therefore, cells develop a variety of mechanisms to repair resulting damaged DNA, but some of these lesions remain and are left to encounter the replication machinery. In addition to having the ability to alter the DNA’s coding potential, DNA lesions present severe blocks to normal DNA replication. How these lesions are replicated has been a key question in the areas of DNA replication, mutagenesis, and carcinogenesis. The answer to this long-standing puzzle has come recently with the discovery of a large group of translesion synthesis DNA polymerases, the Y-superfamily. In this work, I will use a variety of biochemical techniques to examine the molecular mechanisms by which these special DNA polymerases are able to bypass DNA that has been damaged by carcinogens.

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