Title:
Oxidative Damage in DNA: an Exploration of Various DNA Structures

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dc.contributor.advisor Schuster, Gary B.
dc.contributor.author Ndlebe, Thabisile S. en_US
dc.contributor.committeeMember Bridgette Anne Barry
dc.contributor.committeeMember Doyle, Donald F.
dc.contributor.committeeMember Hud, Nicholas V.
dc.contributor.committeeMember Roger M. Wartell
dc.contributor.department Chemistry and Biochemistry en_US
dc.date.accessioned 2006-09-01T19:11:02Z
dc.date.available 2006-09-01T19:11:02Z
dc.date.issued 2006-05-17 en_US
dc.description.abstract Research 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.description.degree Ph.D. en_US
dc.format.extent 7392353 bytes
dc.format.mimetype application/pdf
dc.identifier.uri http://hdl.handle.net/1853/11467
dc.language.iso en_US
dc.publisher Georgia Institute of Technology en_US
dc.subject DNA structures en_US
dc.subject Oxidative damage
dc.subject Charge transport in DNA
dc.subject M-DNA
dc.subject FRET
dc.subject Quadruplex DNA
dc.subject DNA photocleavage
dc.subject Viologen linked acridine derivatives
dc.subject.lcsh DNA Structure en_US
dc.subject.lcsh DNA Analysis en_US
dc.title Oxidative Damage in DNA: an Exploration of Various DNA Structures en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Schuster, Gary B.
local.contributor.corporatename School of Chemistry and Biochemistry
local.contributor.corporatename College of Sciences
relation.isAdvisorOfPublication 5496b90a-0188-49d8-9ec7-fa1ee916e66e
relation.isOrgUnitOfPublication f1725b93-3ab8-4c47-a4c3-3596c03d6f1e
relation.isOrgUnitOfPublication 85042be6-2d68-4e07-b384-e1f908fae48a
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