Computational investigations of alkylation damage to the DNA nucleobase thymine

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dc.contributor.authorBhutani, Priya
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2019-10-29T15:59:38Z
dc.date.available2019-10-29T15:59:38Z
dc.date.issued2019
dc.degree.levelMastersen_US
dc.description.abstractDNA 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.en_US
dc.identifier.urihttps://hdl.handle.net/10133/5564
dc.language.isoen_USen_US
dc.proquest.subject0307en_US
dc.proquest.subject0379en_US
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Department of Chemistry and Biochemistryen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)en_US
dc.subjectalkylationen_US
dc.subjectcomputational chemistryen_US
dc.subjectDNA damageen_US
dc.subjecthuman TLS polymerase etaen_US
dc.subjectthymineen_US
dc.subjectthymine alkylation damageen_US
dc.subjectDissertations, Academicen_US
dc.titleComputational investigations of alkylation damage to the DNA nucleobase thymineen_US
dc.typeThesisen_US
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