A computational investigation of the formation and structure of DNA intrastrand cross-links initiated by the uracil radical

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dc.contributor.authorChurchill, Cassandra D.M
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2012-09-18T17:12:15Z
dc.date.available2012-09-18T17:12:15Z
dc.date.issued2011
dc.degree.levelMasters
dc.descriptionxvi, 147 leaves : ill. (chiefly col.) ; 29 cm + 1 CD-ROMen_US
dc.description.abstractUsing computational methods, the formation pathways and structures of four experimentally-observed DNA intrastrand cross-links are determined. These lesions originate from the uracil radical and are of particular importance due to their potential role in the activity of the 5-halouracils as radiosensitizing agents in anti-tumour treatments. The formation pathways are studied with density functional theory under conditions relevant to both UV and ionizing radiation. Results reveal these intrastrand cross-links are likely to form under therapeutic conditions and provide an explanation for their observed formation preferences. The structures of the cross-links in DNA are determined with molecular dynamics simulations to reveal the distortions these lesions induce to the helix. This has provided information about the potential biological implications of these lesions, where results indicate intrastrand cross-links are likely both mutagenic and cytotoxic. Therefore, these lesions may contribute to tumour cell death in the therapeutic use of halouracils.en_US
dc.identifier.urihttps://hdl.handle.net/10133/3117
dc.language.isoen_USen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry, c2011en_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)en_US
dc.subjectUracil -- Researchen_US
dc.subjectFree radicals (Chemistry) -- Therapeutic use -- Researchen_US
dc.subjectDNA damage -- Researchen_US
dc.subjectDensity functionalsen_US
dc.subjectDissertations, Academicen_US
dc.titleA computational investigation of the formation and structure of DNA intrastrand cross-links initiated by the uracil radicalen_US
dc.typeThesisen_US
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