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Date of Award
Restricted Thesis: Campus only access
Bachelor of Science
Biochemistry & Molecular Biol.
Dr. Michelle L. Hamm
2’-deoxyguanosine (dG) can react with reactive oxygen species (ROS) produced by chemical carcinogens, radiation, and metabolic respiration to form 8-oxo-2’-deoxyguanosine (OdG). While dG inherently base-pairs with 2’-deoxycytidine (dC), OdG can pair with similar stability to either dC or 2’-deoxyadenosine (dA). Should dA be incorporated opposite OdG, the subsequent round of DNA replication will yield the incorporation of dT opposite dA, producing a dG→T transversion. Differences among DNA polymerases’ active sites control the efficiency with which dATP and dCTP are inserted opposite OdG. Incorporation and extension experiments with exonuclease deficient Klenow Fragment (KF-exo; KF-), an A-family polymerase, and human DNA Polymerase β (pol β), an X-family polymerase, were used to investigate these differences. The exact electrostatic and steric characteristics that direct the varying efficiencies of dATP or dCTP incorporation opposite OdG and extension past either OdG:dA or OdG:dC were analyzed using OdG analogues. Results showed that the size of the atom at the C8 position, the protonation of the N7 position, the presence of the C2-exocyclic amine, and interactions between amino acid residues and the XdG:dNTP complex can alter the efficiencies of incorporation and extension with different tolerances seen for KF- and pol β.
McFadden, Emily, "Investigation into the mutagenic potential of 8-oxo-2'-deoxyguanosine (OdG) using KF- and pol β" (2013). Honors Theses. 15.