Computational investigations of alkylation damage to the DNA nucleobase thymine
dc.contributor.author | Bhutani, Priya | |
dc.contributor.author | University of Lethbridge. Faculty of Arts and Science | |
dc.contributor.supervisor | Wetmore, Stacey D. | |
dc.date.accessioned | 2019-10-29T15:59:38Z | |
dc.date.available | 2019-10-29T15:59:38Z | |
dc.date.issued | 2019 | |
dc.degree.level | Masters | en_US |
dc.description.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. | en_US |
dc.identifier.uri | https://hdl.handle.net/10133/5564 | |
dc.language.iso | en_US | en_US |
dc.proquest.subject | 0307 | en_US |
dc.proquest.subject | 0379 | en_US |
dc.proquestyes | Yes | en_US |
dc.publisher | Lethbridge, Alta. : University of Lethbridge, Department of Chemistry and Biochemistry | en_US |
dc.publisher.department | Department of Chemistry and Biochemistry | en_US |
dc.publisher.faculty | Arts and Science | en_US |
dc.relation.ispartofseries | Thesis (University of Lethbridge. Faculty of Arts and Science) | en_US |
dc.subject | alkylation | en_US |
dc.subject | computational chemistry | en_US |
dc.subject | DNA damage | en_US |
dc.subject | human TLS polymerase eta | en_US |
dc.subject | thymine | en_US |
dc.subject | thymine alkylation damage | en_US |
dc.subject | Dissertations, Academic | en_US |
dc.title | Computational investigations of alkylation damage to the DNA nucleobase thymine | en_US |
dc.type | Thesis | en_US |