{"id":{"repo_id":"lethbridge","oai_identifier":"oai:opus.uleth.ca:10133/5564"},"canonical_url":"https://search.dev.ndltd.org/etd/lethbridge/oai:opus.uleth.ca:10133/5564","repository":{"repo_id":"lethbridge","name":"University of Lethbridge","base_url":"https://opus.uleth.ca/server/oai/request"},"display":{"title":"Computational investigations of alkylation damage to the DNA nucleobase thymine","abstract":"DNA alkylation damage is caused by numerous sources in the environment. Alkylation damage can stall standard DNA polymerases and replication instead occurs through a process called translesion synthesis (TLS). This thesis uses a combination of density functional theory calculations and molecular dynamics simulations to rationalize the mutagenic patterns of O-alkylthymine adducts and elucidate the role of human TLS polymerase η in their replication. Specifically, this thesis unveils the effect of alkyl chain position by considering O2-methylthymine and O4-methylthymine. Furthermore, the impact of alkyl chain size is revealed by studying the O4-[4-(3-pyridyl)-4-oxobut-1-yl]-thymine lesion, which is derived from tobacco smoke. Finally, insight into the impact of alkyl chain shape is obtained by considering the synthetic O2-n-butylthymine and O2-iso-butylthymine adducts. Overall, this thesis addresses some of the unanswered questions surrounding the replication of thymine alkylation damage and provides a better understanding of human polymerase η that has been implicated in disease.","abstract_html":"DNA alkylation damage is caused by numerous sources in the environment. Alkylation damage can stall standard DNA polymerases and replication instead occurs through a process called translesion synthesis (TLS). This thesis uses a combination of density functional theory calculations and molecular dynamics simulations to rationalize the mutagenic patterns of O-alkylthymine adducts and elucidate the role of human TLS polymerase η in their replication. Specifically, this thesis unveils the effect of alkyl chain position by considering O2-methylthymine and O4-methylthymine. Furthermore, the impact of alkyl chain size is revealed by studying the O4-[4-(3-pyridyl)-4-oxobut-1-yl]-thymine lesion, which is derived from tobacco smoke. Finally, insight into the impact of alkyl chain shape is obtained by considering the synthetic O2-n-butylthymine and O2-iso-butylthymine adducts. Overall, this thesis addresses some of the unanswered questions surrounding the replication of thymine alkylation damage and provides a better understanding of human polymerase η that has been implicated in disease.","abstract_has_math":false,"creators":["Bhutani, Priya","University of Lethbridge. Faculty of Arts and Science"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019","date_published":"2019","updated_at":"2026-07-27T20:02:20Z","subjects":["alkylation","computational chemistry","DNA damage","human TLS polymerase eta","thymine","thymine alkylation damage","Dissertations, Academic"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10133/5564"],"render_values":[{"text":"hdl:10133/5564","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":["2019"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["alkylation","computational chemistry","DNA damage","human TLS polymerase eta","thymine","thymine alkylation damage","Dissertations, Academic"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10133/5564"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.other","label":"Dc Description Other","values":["DNA alkylation damage is caused by numerous sources in the environment. Alkylation damage can stall standard DNA polymerases and replication instead occurs through a process called translesion synthesis (TLS). This thesis uses a combination of density functional theory calculations and molecular dynamics simulations to rationalize the mutagenic patterns of O-alkylthymine adducts and elucidate the role of human TLS polymerase η in their replication. Specifically, this thesis unveils the effect of alkyl chain position by considering O2-methylthymine and O4-methylthymine. Furthermore, the impact of alkyl chain size is revealed by studying the O4-[4-(3-pyridyl)-4-oxobut-1-yl]-thymine lesion, which is derived from tobacco smoke. Finally, insight into the impact of alkyl chain shape is obtained by considering the synthetic O2-n-butylthymine and O2-iso-butylthymine adducts. Overall, this thesis addresses some of the unanswered questions surrounding the replication of thymine alkylation damage and provides a better understanding of human polymerase η that has been implicated in disease."]},{"key":"dc:title","label":"Title","values":["Computational investigations of alkylation damage to the DNA nucleobase thymine"]}]}],"canonical_facts":{"dc:date.issued":["2019"],"dc:description.other":["DNA alkylation damage is caused by numerous sources in the environment. Alkylation damage can stall standard DNA polymerases and replication instead occurs through a process called translesion synthesis (TLS). This thesis uses a combination of density functional theory calculations and molecular dynamics simulations to rationalize the mutagenic patterns of O-alkylthymine adducts and elucidate the role of human TLS polymerase η in their replication. Specifically, this thesis unveils the effect of alkyl chain position by considering O2-methylthymine and O4-methylthymine. Furthermore, the impact of alkyl chain size is revealed by studying the O4-[4-(3-pyridyl)-4-oxobut-1-yl]-thymine lesion, which is derived from tobacco smoke. Finally, insight into the impact of alkyl chain shape is obtained by considering the synthetic O2-n-butylthymine and O2-iso-butylthymine adducts. Overall, this thesis addresses some of the unanswered questions surrounding the replication of thymine alkylation damage and provides a better understanding of human polymerase η that has been implicated in disease."],"dc:identifier":["hdl:10133/5564"],"dc:subject":["alkylation","computational chemistry","DNA damage","human TLS polymerase eta","thymine","thymine alkylation damage","Dissertations, Academic"],"dc:title":["Computational investigations of alkylation damage to the DNA nucleobase thymine"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T20:02:20Z"}