Properties of C-linked C8-phenoxyl guanine DNA adducts

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dc.contributor.authorMillen, Andrea
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2013-11-27T21:10:22Z
dc.date.available2013-11-27T21:10:22Z
dc.date.issued2011
dc.descriptionxix, 192 leaves : ill. (some col.) ; 29 cmen_US
dc.description.abstractDNA damage is important to understand since it has the potential to lead to disease if unrepaired. In particular, bulky C8 guanine adducts (addition products) are known to induce a variety of mutations due to their conformational flexibility. C-linked C8-phenoxyl-deoxyguanosine adducts (PhOH-dG) have been poorly understood despite their potential for genotoxicity. This thesis systematically develops a computational model to predict the conformational and base-pairing preferences of PhOH-dG by gradually increasing the size of the system. The structure of PhOH-dG in DNA is determined, where the bulky C8 group induces a syn conformation of the base similar to other C8-adducts. A stabilized guanine mismatch is identified for the syn adducts, which implies that the primary mechanism of genotoxicity may be base-substitution mutations resulting in G→C transversions. This thesis has contributed to a growing body of literature dedicated to understanding the role of conformational heterogeneity in the mutagenicity of bulky C8-adducts.en_US
dc.identifier.urihttps://hdl.handle.net/10133/3312
dc.language.isoen_CAen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry, c2011en_US
dc.publisher.departmentDepartment of Chemistry & Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.subjectDNA damage -- Researchen_US
dc.subjectDNA adducts -- Researchen_US
dc.subjectDNA adducts -- Computer simulationen_US
dc.subjectGenetic toxicology -- Researchen_US
dc.subjectMutagenesisen_US
dc.subjectPhenoxy groupsen_US
dc.subjectRadicals (Chemistry)en_US
dc.titleProperties of C-linked C8-phenoxyl guanine DNA adductsen_US
dc.typeThesisen_US
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