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Author

Kevin Kindler

Date of Award

Spring 2013

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Chemistry

First Advisor

Dr. Michelle L. Hamm

Abstract

In the presence of oxidative stress, the DNA nucleotide 2’-deoxyguanosine (dG) can be converted to 8-oxo-2’-deoxyguanosine (OdG). OdG can base pair with 2’-deoxycytidine (dC), but it can also pair with 2’-deoxyadensoine (dA) to form another stable pairing. Past research has shown that certain polymerases have difficulty distinguishing between the OdG:dC and OdG:dA base pairs. This can be problematic because instead of pairing OdG to dC, which causes no mutation, the OdG instead pairs to dA which can result in a dG to dT transversion. For these reasons, OdG is pro-mutagenic, increasing in frequency both with normal aging and when diseased. The large fragment of polymerase I from Bacillus stearthermophilus (BF) is a prime polymerase to study the mutagenic potential of OdG because it has solved crystal structures with OdG in the extension site. It also lacks proofreading exonuclease sites, which simplifies the analysis of the replication past the analogues. The incorporation of and extension past dCTP and dATP opposite numerous analogues of dG and OdG by BF was studied in order to determine the importance of the C8-oxygen and C2-exocyclic amine to OdG mutagenicity.

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