Conformational analysis of DNA damaged by aristolochic acids to assess the toxicity and repair : a computational study

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dc.contributor.authorKathuria, Preetleen
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2015-09-10T22:18:49Z
dc.date.available2015-09-10T22:18:49Z
dc.date.issued2015
dc.degree.levelMastersen_US
dc.description.abstractMolecular modeling study is carried out on DNA damaged by aristolochic acids I and II. The carcinogenic effects of these acids have been attributed to the formation of bulky adducts within DNA (specifically with the adenine and guanine nucleobases). The analysis is initiated by considering the conformational preferences of the aristolochic acid adducts in small models (nucleobase, nucleoside and nucleotide) using quantum mechanical calculations. Subsequently, the adducts were studied using molecular dynamics simulations at the oligonucleotide level by incorporating the damaged base in an 11-mer DNA strand. The structural preferences of adenine and guanine adducts are compared, which may explain the experimentally-observed differential repair propensity. Finally, sequence-induced differences in the structural features of adducted DNA containing the ALI-adenine lesion are analyzed to explain the experimentally-reported higher mutagenicity of the lesion in a particular sequence. Results and implications from each of these studies are presented, and future research directions are proposed.en_US
dc.description.sponsorshipNatural Sciences and Engineering Research Council of Canada [249598-07]; Canada Research Chain Program [950-228175]; Canadian Foundation of Innovation [22770]; University of Lethbridge Research Fund [13368].en_US
dc.embargoNoen_US
dc.identifier.urihttps://hdl.handle.net/10133/3744
dc.language.isoen_CAen_US
dc.proquest.subject0494en_US
dc.proquestyesYesen_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.subjectadenine adductsen_US
dc.subjectaristolochic acid purine adductsen_US
dc.subjectcomputational modelsen_US
dc.subjectdensity functional theoryen_US
dc.subjectguanine adductsen_US
dc.subjectmutagenesisen_US
dc.titleConformational analysis of DNA damaged by aristolochic acids to assess the toxicity and repair : a computational studyen_US
dc.typeThesisen_US
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