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Date of Award

4-30-2021

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Dr. Michelle Hamm

Abstract

8-oxo-2’-deoxyguanosine, or OdG, is a DNA lesion that arises as a result of a reaction between 2’-deoxyguanosine (dG) and reactive oxygen species (ROS). OdG lesions can cause the development of various health complications, including but not limited to cancer and rheumatoid arthritis. OdG can form base pairs with 2’-deoxycytidine (dC), which is what normally occurs with dG base pairing. However, OdG can also mispair with 2’-deoxyadenosine (dA), which leads to a dG to 2’-deoxythymidine (dT) mutation. Prior work in the Hamm lab with a fragment of the A-family polymerase I from Thermus aquaticus (KT) showed that the presence of a sulfur off the C8-position of dG (SdG) directs increased efficiency of dCTP incorporation as compared to OdG. In this work, a mutant version of KT (KT R675S) was studied to better understand the major groove interactions of OdG with KT, as well as to investigate what might be the source of the increased dCTP incorporation efficiency opposite SdG and SdI. Investigations with various analogs of OdG indicated that the R675S mutation did not significantly affect dCTP incorporations opposite OdG or SdG. However, the studies did indicate a potential major groove clash between the C2-amine of OdG and R675 during dATP incorporation.

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