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dc.contributor.authorNdlebe, Thabisile S.en_US
dc.date.accessioned2006-09-01T19:11:02Z
dc.date.available2006-09-01T19:11:02Z
dc.date.issued2006-05-17en_US
dc.identifier.urihttp://hdl.handle.net/1853/11467
dc.description.abstractResearch efforts to determine the causes, effects and locations of mutations within the human genome have been widely pursued due to their role in the development of various diseases. The main cause of mutations in vivo is oxidative damage to DNA via oxidants and free radical species. Numerous studies have been performed in vitro to determine how oxidative damage is induced in DNA. Most of these in vitro studies require photosensitizers to initiate the oxidative damage through various mechanisms. For the purposes of this research, all the photosensitizers that were used initiated oxidative damage in DNA through the electron transfer mechanism. In the charge transport studies, an anthraquinone photosensitizer was covalently linked to the 5 end of DNA by a short carbon tether in order to determine the pattern of damage induced along the length of the DNA. Anthraquinone preferentially damages guanine bases. Our first work sought to determine the effects of charge transport through guanine rich quadruplex DNA dimers. The dimers were formed by the combination of two hairpins with duplex overhangs extending beyond the quadruplex region. This enabled the optimal comparison of the effects of charge transport between duplex and quadruplex DNA structures. Another area of research we pursued in this area was to determine the effects of charge transport in M-DNA (a novel DNA conformation that was reported to form in the presence of zinc ions at a pH above 8). Earlier work on M-DNA suggested that it behaved like a molecular wire. Our research attempted to determine the effects of charge transport on this structure in order to show the behavior of a DNA molecular wire as compared to the standard studies performed in this area on normal B-DNA structures. Lastly, in collaboration with Dr. Ramaiah and colleagues we designed some viologen linked acridine photosensitizers which were tested for any ability to cleave GGG bulges. In preliminary studies, these viologen linked acridine derivatives showed preferential cleavage for guanine bases. They were not covalently bound to DNA, although they could potentially form non covalent interactions with DNA such as intercalation and/or groove binding. Our overall research goal was to determine the extent and overall effect of oxidative damage (using different photosensitizers) on the various DNA structures mentioned above.en_US
dc.format.extent7392353 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherGeorgia Institute of Technologyen_US
dc.subjectDNA structuresen_US
dc.subjectOxidative damage
dc.subjectCharge transport in DNA
dc.subjectM-DNA
dc.subjectFRET
dc.subjectQuadruplex DNA
dc.subjectDNA photocleavage
dc.subjectViologen linked acridine derivatives
dc.subject.lcshDNA Structureen_US
dc.subject.lcshDNA Analysisen_US
dc.titleOxidative Damage in DNA: an Exploration of Various DNA Structuresen_US
dc.typeDissertationen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentChemistry and Biochemistryen_US
dc.description.advisorCommittee Chair: Dr. Gary B. Schuster; Committee Member: Bridgette Anne Barry; Committee Member: Donald F. Doyle; Committee Member: Nicholas V. Hud; Committee Member: Roger M. Wartellen_US


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