Properties of C-linked C8-phenoxyl guanine DNA adducts

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.

Author

• Millen, Andrea

• DNA damage -- Research
• DNA adducts -- Research
• DNA adducts -- Computer simulation
• Genetic toxicology -- Research
• Mutagenesis
• Phenoxy groups
• Radicals (Chemistry)

Identifier

hdl:10133/3312

OAI identifier oai:identifier

oai:opus.uleth.ca:10133/3312