Computational investigation of oxidative damage to guanine: formation, recognition and removal by DNA repair enzymes in humans and bacteria

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dc.contributor.authorSowlati-Hashjin, Shahin
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2018-05-02T15:25:01Z
dc.date.available2018-05-02T15:25:01Z
dc.date.issued2018
dc.degree.levelPh.Den_US
dc.description.abstractFormation of guanine oxidation products is among the most frequently occurring DNA damaging events, and has been suspected to be related to aging, Alzheimer’s disease and various types of cancer. Guanine oxidative products are removed and replaced through the base excision repair (BER) pathway, which involves several enzymes including DNA glycosylases. BER is initiated when a DNA glycosylase detects a lesion and removes the damaged nucleobase. The present thesis employs computational chemistry to investigate the formation mechanisms of two guanine oxidation products, namely 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 7,8-dihydro-8-oxoguanine (OG). Moreover, several steps during the repair processes catalyzed by human (hOgg1) and bacterial (FPG) DNA glycosylases, including the lesion recognition, base removal, DNA backbone cleavage, and hydrolysis of the resulting DNA‒enzyme complex, are investigated using quantum mechanical and molecular dynamics approaches. The atomic-level details provided by these calculations show the differences in the recognition and removal mechanisms catalyzed by human and bacterial glycosylases.en_US
dc.embargoNoen_US
dc.identifier.urihttps://hdl.handle.net/10133/5093
dc.language.isoen_USen_US
dc.proquest.subject0485en_US
dc.proquest.subject0487en_US
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta. : Universtiy 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.subjectDNA repairen_US
dc.subjectDNA repair--Computer simulationen_US
dc.subjectDNA damageen_US
dc.subjectOxidationen_US
dc.subjectoxidation of guanineen_US
dc.subjectbase excision repairen_US
dc.subjectcomputer modellingen_US
dc.subjectDNA glycosylasesen_US
dc.titleComputational investigation of oxidative damage to guanine: formation, recognition and removal by DNA repair enzymes in humans and bacteriaen_US
dc.typeThesisen_US
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