Date of Graduation

Fall 2011

Degree

Master of Science in Chemistry

Department

Chemistry and Biochemistry

Committee Chair

Gary Meints

Abstract

Nucleic acids encode the genetic information in all organisms. In order for this information to be passed it is necessary for DNA to be able to interact properly with proteins. This protein-DNA interaction can be interrupted if there is damage within the DNA sequence. Therefore, DNA damage can have severe consequences such as aging, cancer, as well as other serious health problems. The specific damage being investigated is 1,N6 -Ethenodeoxyadenosine (EA).EA is formed by reaction with lipid peroxidation products or reaction with vinyl chloride metabolites. This particular type of lesion is repaired via base excision repair (BER) pathway or direct repair pathway, of which nucleotide flipping of the damaged site is a key part. The enzyme involved with BER is AAG, and the enzyme responsible for direct repair is ABH2. It is the aim of this project to determine if the local structural conformation and local dynamics in the DNA backbone are different if a lesion is present. If there is a significant difference in conformation it could point to a possible recognition mechanism for the DNA glycoslyase, and lead to a better understanding of the BER pathway. I am investigating this hypothesis using 1D and 2D 1H solution NMR techniques. It was found that there was a significant shift in the protons both on the sugar ring of the lesion and the sugar rings of the bases near the lesion.

Keywords

Ethenodeoxyadenosine, NMR, DNA Repair, DNA, BER, Direct Repair

Subject Categories

Chemistry

Copyright

© Brianna Medrano

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