Computational investigation of the mechanism of action of DNA glycosylases

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dc.contributor.authorKellie, Jennifer L.
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2014-10-30T21:30:37Z
dc.date.available2014-10-30T21:30:37Z
dc.date.issued2013
dc.degree.levelPh.Den_US
dc.descriptionxix, 390 leaves : ill. (chiefly col.) ; 29 cm + 1 CD-ROM
dc.description.abstractThe integrity of the base pair sequence that makes up the information storage system of cells is under continual assault. Two of the most prevalent forms of nucleobase damage are conversion of cytosine to uracil, and guanine to 8-oxoguanine. Repair of these lesions is initiated by a specific glycosylase that hydrolyzes the N-glycosidic (sugar–nucleobase) bond of the damaged nucleotide. The present thesis uses advanced computational chemistry techniques to study the mechanism of action of three glycosylases, namely human uracil–DNA glycosylase (hUNG2), adenine–DNA glycosylase (MutY) and human 8-oxoguanine–DNA glycosylase (hOgg1). Truncated active-site models treated entirely with quantum mechanics, and reaction potential energy surfaces, provide detailed structural and energetic information regarding how these enzymes catalyze deglycosylation of their substrates. From these results, a novel and informative method for predicting the mechanism (e.g., degree of asychronicity) and relative rate is proposed.en_US
dc.identifier.urihttps://hdl.handle.net/10133/3598
dc.language.isoen_CAen_US
dc.proquestyesNoen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. 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.subjectbase pair sequenceen_US
dc.subjectnucleobase damageen_US
dc.subjecturacilen_US
dc.subject8-oxoguanineen_US
dc.subjecthUNG2en_US
dc.subjectMutYen_US
dc.subjecthOgg1en_US
dc.subjectDNA repair
dc.subjectDNA damage
dc.subjectDNA ligases
dc.subjectDeamination
dc.subjectDissertations, Academic
dc.titleComputational investigation of the mechanism of action of DNA glycosylasesen_US
dc.typeThesisen_US
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