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Date of Award

2015

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biochemistry & Molecular Biol.

First Advisor

Dr. Eugene Wu

Abstract

Cyclobutane Pyrimidine Dimers (CPDs) are photolesions that form when UV-­‐B irradiation causes adjacent thymine or cytosine bases to covalently bond. These structures can arrest DNA synthesis by replicative polymerases, as they induce local helical distortions in the template strand that inhibit nucleotide incorporation. The primary goal of this study was to gain better insight into the effects of thymine dimers (T^T) on DNA replication in a model polymerase. Here, we present kinetic studies along with crystal structures of the Bacillus DNA polymerase I large fragment in complex with a CPD-­‐containing template and an incoming dNTP. Together, our results suggest a mechanism by which CPDs can inhibit DNA synthesis in Bacillus DNA pol.

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