Computational studies of interstrand crosslink formation in DNA

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dc.contributor.authorTakyi, Nathania
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2023-01-24T19:24:00Z
dc.date.available2023-01-24T19:24:00Z
dc.date.issued2022
dc.degree.levelMastersen_US
dc.description.abstractInterstrand crosslinks (ICLs) are toxic DNA lesions that can result in cell death if left unrepaired. ICLs can form following the reaction of natural DNA nucleobases with reactive chemical species generated during DNA repair. This thesis uses computational methods to investigate ICL formation resulting from the reaction of DNA repair intermediates with DNA nucleobases. Molecular dynamics (MD) simulations are used to provide an explanation for the effects of sequence context on the yield of ICLs that form following attempted repair of 1,N6-ethenoadenosine by alpha-ketoglutarate dependent dioxygenase homolog 2 (ALKBH2). Subsequently, an explanation for the preference of different Ap-derived ICLs is provided using density functional theory (DFT) calculations and MD simulations. Finally, the effect of sequence context on the dA-Ap ICL yield is investigated using MD simulations. Overall, this thesis uses molecular modelling approaches to rationalize how sequence context affects ICL yield and reveals the role of the structure of damaged DNA in ICL formation.en_US
dc.description.sponsorshipUniversity of Lethbridge School of Graduate Studies NSERC CREATE RNA Innovationen_US
dc.identifier.urihttps://hdl.handle.net/10133/6418
dc.language.isoen_USen_US
dc.proquest.subject0487en_US
dc.proquest.subject0221en_US
dc.proquest.subject0485en_US
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistryen_US
dc.publisher.departmentDepartment of Chemistry & Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)en_US
dc.subjectDamaged DNA
dc.subjectInterstrand crosslinks
dc.subjectICL formation
dc.subjectMolecular modelling
dc.subjectDNA lesions
dc.subject.lcshDNA repair
dc.subject.lcshMolecules--Models
dc.subject.lcshMolecular dynamics
dc.subject.lcshComputational chemistry
dc.subject.lcshDissertations, Academic
dc.titleComputational studies of interstrand crosslink formation in DNAen_US
dc.typeThesisen_US
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