{"id":{"repo_id":"lethbridge","oai_identifier":"oai:opus.uleth.ca:10133/3312"},"canonical_url":"https://search.dev.ndltd.org/etd/lethbridge/oai:opus.uleth.ca:10133/3312","repository":{"repo_id":"lethbridge","name":"University of Lethbridge","base_url":"https://opus.uleth.ca/server/oai/request"},"display":{"title":"Properties of C-linked C8-phenoxyl guanine DNA adducts","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Millen, Andrea"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011","date_published":"2011","updated_at":"2026-07-27T20:02:45Z","subjects":["DNA damage -- Research","DNA adducts -- Research","DNA adducts -- Computer simulation","Genetic toxicology -- Research","Mutagenesis","Phenoxy groups","Radicals (Chemistry)"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10133/3312"],"render_values":[{"text":"hdl:10133/3312","href":null,"code":true}]}]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2011"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["DNA damage -- Research","DNA adducts -- Research","DNA adducts -- Computer simulation","Genetic toxicology -- Research","Mutagenesis","Phenoxy groups","Radicals (Chemistry)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10133/3312"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.other","label":"Dc Description Other","values":["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."]},{"key":"dc:title","label":"Title","values":["Properties of C-linked C8-phenoxyl guanine DNA adducts"]}]}],"canonical_facts":{"dc:date.issued":["2011"],"dc:description.other":["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."],"dc:identifier":["hdl:10133/3312"],"dc:subject":["DNA damage -- Research","DNA adducts -- Research","DNA adducts -- Computer simulation","Genetic toxicology -- Research","Mutagenesis","Phenoxy groups","Radicals (Chemistry)"],"dc:title":["Properties of C-linked C8-phenoxyl guanine DNA adducts"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T20:02:45Z"}