Investigating Local Motions in Damaged DNA Base Pairs Using Solid State NMR

Date of Graduation

Summer 2006

Degree

Master of Science in Chemistry

Department

Chemistry and Biochemistry

Committee Chair

Gary A. J. Meints

Abstract

Maintenance of the proper structure of DNA is essential for the health of all organisms. Damage to DNA structure in humans can lead to serious health problems such as Alzheimer’s disease and cancer, and is implicated in the aging process. To combat the damage that inevitably occurs at the molecular level, a sophisticated repair process is present to help maintain the integrity of DNA. This process involves a series of DNA repair enzymes, and contains several steps: 1) Identification of the DNA damage by repair enzyme, 2) binding of the repair enzyme to the damaged DNA, 3) removal of the damaged part of the DNA, and 4) cutting the DNA strand to allow for proper DNA replication. The final three steps in the process are well understood, but interestingly, the process by which the repair enzymes identify the DNA damage is not. Increased motion at the location of the damage has been suggested as a major factor in how repair enzymes identify damage to DNA. Solid-state deuterium nuclear magnetic resonance (NMR) is an experimental technique that is adept at analyzing molecular motions in numerous kinds of molecules, and has been used extensively in studies of undamaged DNA. This project utilizes this technique to investigate changes in DNA motions caused by oxidation of guanine to 8-oxoguanine, a form of damage known to instigate carcinogenesis. Deuterated eoxyribonucleoside derivatives of guanine and 9-oxoguanine will be synthesized and incorporated into several DNA molecules. Results from NMR experiments for each of these DNAs will be compared to determine any effect the damage has on a local motions. Results from this work will lead to a greater understanding of the cellular mechanism that not only repairs mutagenic damage to DNA, but also maintains the integrity of our genetic code.

Keywords

DNA, NMR, repair enzymes, oxidative damage, BER

Subject Categories

Cellular and Molecular Physiology | Chemistry

Copyright

© Monica Nicole Kinde-Carson

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Dissertation/Thesis

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