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. / xix, 192 leaves : ill. (some col.) ; 29 cm
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:ALU.w.uleth.ca/dspace#10133/3312 |
| Date | January 2011 |
| Creators | Millen, Andrea |
| Contributors | Wetmore, Stacey |
| Publisher | Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry, c2011, Arts and Science, Department of Chemistry & Biochemistry |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_CA |
| Detected Language | English |
| Type | Thesis |
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