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dc.contributor.advisorThomas, Douglas D.en_US
dc.contributor.authorMikhed, Yuliyaen_US
dc.date.accessioned2012-12-10T16:44:11Z
dc.date.available2012-12-10T16:44:11Z
dc.date.created2012-05en_US
dc.date.issued2012-12-10
dc.date.submitted2012-05en_US
dc.identifier.urihttp://hdl.handle.net/10027/9167
dc.description.abstractDNA methylation is an epigenetic process that affects gene silencing, genomic imprinting and X-chromosome inactivation. Aberrant methylation is associated with imprinting-related diseases, DNA mutations, and cancer. Aberrant DNA methylation activates certain repair mechanisms such as Direct Reversal (DRR). In mammalian cells, human AlkB homolog 2 (ABH2) is the major housekeeping enzyme in this pathway. Its function is to remove a methyl group from the 1st position on adenine and/or 3rd position on cytosine in double-stranded DNA. Alkylating antineoplastic agents can act via methylating DNA and therefore inhibition of DNA repair machinery, such as Fe(II)-dependent enzymes, like ABH2, might augment this treatment. For this reason iron chelators have emerged as potential anti cancer drugs for their ability to inhibit this class of DNA repair enzymes. Recently our group has shown that nitric oxide can sequester cellular iron in the form of dinitrosyliron complexes. Hence, we hypothesized that nitric oxide could inhibit ABH2 though interaction with iron leading to inhibition of methylated DNA repair. To test this, we developed a novel in vitro method of detection for ABH2 activity. This method consists of measuring ABH2 activity using methylated DNA followed by detection with quantitative real-time PCR (qRT-PCR) analysis. The major advantage of this method is the ability to avoid known obstacles associated with other detection methods, like radioactivity. Also it provides specific, robust, and accurate results. Using this technique we have shown that nitric oxide can effectively inhibit the demethylation activity of ABH2. These results indicate that nitric oxide or nitric oxide generating compounds might be an important adjuvant therapy to existing chemotherapeutic alkylating agents.en_US
dc.language.isoenen_US
dc.rightsCopyright 2012 Yuliya Mikheden_US
dc.subjectnitric oxideen_US
dc.subjectDNA repair enzymeen_US
dc.subjecthABH2en_US
dc.subjectdioxygenaseen_US
dc.subjectHuman AlkB homologue 1-8en
dc.titleEffect of Nitric Oxide on DNA Repair Dioxygenase - Human AlkB Homolog 2en_US
thesis.degree.departmentMedicinal Chemistry and Pharmacognosyen_US
thesis.degree.disciplineMedicinal chemistryen_US
thesis.degree.grantorUniversity of Illinois at Chicagoen_US
thesis.degree.levelMastersen_US
thesis.degree.nameMS, Master of Scienceen_US
dc.type.genrethesisen_US
dc.type.materialtexten_US


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