Properties of C-linked C8-phenoxyl guanine DNA adducts
dc.contributor.author | Millen, Andrea | |
dc.contributor.supervisor | Wetmore, Stacey D. | |
dc.date.accessioned | 2013-11-27T21:10:22Z | |
dc.date.available | 2013-11-27T21:10:22Z | |
dc.date.issued | 2011 | |
dc.description | xix, 192 leaves : ill. (some col.) ; 29 cm | en_US |
dc.description.abstract | DNA 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.uri | https://hdl.handle.net/10133/3312 | |
dc.language.iso | en_CA | en_US |
dc.publisher | Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry, c2011 | en_US |
dc.publisher.department | Department of Chemistry & Biochemistry | en_US |
dc.publisher.faculty | Arts and Science | en_US |
dc.subject | DNA damage -- Research | en_US |
dc.subject | DNA adducts -- Research | en_US |
dc.subject | DNA adducts -- Computer simulation | en_US |
dc.subject | Genetic toxicology -- Research | en_US |
dc.subject | Mutagenesis | en_US |
dc.subject | Phenoxy groups | en_US |
dc.subject | Radicals (Chemistry) | en_US |
dc.title | Properties of C-linked C8-phenoxyl guanine DNA adducts | en_US |
dc.type | Thesis | en_US |