Date of Graduation

Summer 2009

Degree

Master of Science in Chemistry

Department

Chemistry

Committee Chair

Gary Meints

Keywords

DNA, 8-oxogunaine, BER, repair enzymes, [34]P NMR

Subject Categories

Chemistry

Abstract

Through normal aerobic metabolism, reactive oxygen species (ROS) are formed as byproducts and react with DNA. The interaction of DNA with ROS results in the oxidation of guanine producing 8-oxoguanine, which has been linked to aging, Alzheimer's disease, and various forms of cancer. The repair process, Base Excision Repair (BER), protects the integrity of the DNA and prevents mutations on a molecular level. BER employs repair enzymes to identify and bind with the damaged DNA base site, remove it from its helical position, and cut it from the DNA strand before inserting the proper base. The latter two steps are well understood, with the process of the identification of the damaged DNA base in question. The difference between a proper DNA base compared to a damaged DNA base may be structurally minimal, but the process has proved to be efficient and precise. In the case of 8-oxoguanine, which structurally differs from guanine by an oxygen atom, the 8-oxoguanine DNA glycosylase (hOGG1) identifies the damaged base in the vast majority of guanine bases. We propose that a conformational change occurs to the DNA phosphate backbone that contains the 8-oxoguanine to aid in its identification. Through the means of phosphorus (31P) NMR and 31P chemical shifts, we were able to study the 31P atoms present in the DNA backbone in order to determine conformational changes. A comparative study was employed to analyze the differences in 31P chemical shifts between proper DNA and DNA containing 8-oxoguanine. The changes in the 31P chemical shifts are then directly related to any conformational exchanges occurring between the DNA samples. The results of this study have contributed to the overall understanding of the recognition process in BER.

Copyright

© Mallory Elaine Clark

Campus Only

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