Date of Graduation

Summer 2026

Degree

Master of Science in Chemistry

Department

Chemistry & Biochemistry

Committee Chair

Gary, Meints

Abstract

Base excision repair (BER) mechanisms fix single base lesions in DNA, such as T:G mismatches. During the base excision repair mechanism, an abasic site (AP site) is formed as an intermediate. AP sites are unstable and highly mutagenic; they can stop DNA replication. This research investigates how the conformational properties of abasic sites in DNA affect the binding recognition of enzymes involved in DNA repair mechanisms, including BER. Three different abasic sequences are being analyzed for this research project. A second project looks at the effects of a naturally occurring purine derivative, hypoxanthine, on the DNA backbone. These hypoxanthine lesions are also repaired by the BER mechanism. Using 1H NOESY, 31P HSQC, and 1D 31P NMR experiments, values can be obtained associated with the energy barriers and the regulatory energy of each phosphate conformational state such as BI and BII. The 1H NOESY experiment gives information about the structural position of the hydrogen molecules in the DNA sequence. From this research it was found that both the presence of abasic sites and hypoxanthine lead to significant perturbations of the DNA backbone dynamics. This data will help us to understand better the BER mechanism and how the abasic site and hypoxanthine affect the DNA backbone.

Keywords

Base Excision Repair, DNA, abasic site, hypoxanthine, Nuclear Magnetic Resonance Spectroscopy, conformational state, BI/BII

Subject Categories

Biochemistry | Physical Chemistry

Copyright

© Clarissa R. Krimmel

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