Date of Graduation

Spring 2011

Degree

Master of Science in Chemistry

Department

Chemistry

Committee Chair

Gary Meints

Keywords

deoxyribonucleic acid, base excition repair, ethenodeoxyadenosine, deutrium solid-state nuclear magnetic resonance, magic angle spinning

Subject Categories

Chemistry

Abstract

Nucleic acids are essential for all cellular machinery to operate properly. Deoxyribonucleic acid (DNA) acts as a molecular repository, storing and transmitting all genetic information. It is essential that DNA maintain its structural integrity to ensure the replication process occurs flawlessly. Damage to DNA can alter its sequence and shape, thereby hindering the ability to effectively transmit genetic information. Left unrepaired, damaged DNA can lead to cancer and other serious health problems. The particular type of DNA damage being investigated is the etheno (Ɛ) base adduct, 1,N6-etheno-2'-deoxyadenosine. This is formed during exposure to vinyl chloride, a known carcinogen used widely in the production of polyvinyl chloride (PVC). The Ɛ-adducts are eliminated through base excision repair (BER), with DNA glycosylases being the key enzymes of this pathway. Although the final steps of BER are well characterized, what remains unclear is how the repair enzymes identify the damaged base. It has been proposed that an increase in motions occurs at the damage site to aid in the recognition process of the repair enzymes. Solid-state deuterium nuclear magnetic resonance with magic angle spinning is an effective tool used to analyze molecular motions in small samples of DNA. By employing a full hydration level study of the synthetic oligonucleotide containing [2"-2H]-deoxyadenosine the local motions taking place in the furanose ring are understood. The results of this study will be the baseline for a future comparative study between DNA containing the etheno base adduct and proper DNA.

Copyright

© Sarah Elizabeth Nichols

Campus Only

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