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Date of Award
2020
Document Type
Restricted Thesis: Campus only access
Degree Name
Bachelor of Science
Department
Biochemistry & Molecular Biol.
First Advisor
Dr. Michelle Hamm
Abstract
8-Oxo-2’-deoxyguanosine (OdG) is a specific DNA lesion that originates from the reaction between reactive oxygen species (ROS) and 2’-deoxyguanosine (dG). OdG can form stable base pairs not only with dC, as is typical, but also with dA. The latter pair is a mismatch that can lead to a dG to dT transversion mutation in DNA. dG to dT mutations, like those caused by OdG, have been linked to cancer, ageing, and other negative processes. In this work, we studied human Y-family bypass polymerase kappa (hPolκ) to better understand its preference for dATP incorporation opposite OdG. Based on the crystal structure of hPolκ, it has been suggested that it has a rigid insertion site which prefers OdG in the syn conformation. Different analogues of OdG were used to study the effects of steric bulk off the C8-position, as well as the C2-exocyclic amine on its mutagenic potential. The addition of a large atom at the C8-position and the removal of the C2-amine both lead to decreased dCTP incorporation efficiency, thus increasing the mutagenic potential of OdG and its analogues. There was no clear effect on dATP incorporation when the C8- or C2-substituents were altered.
Recommended Citation
Zielinski, Samuel, "Investigations into the mutagenic potential of 8-oxo-2’-deoxyguanosine with human polymerase κ" (2020). Honors Theses. 1522.
https://scholarship.richmond.edu/honors-theses/1522