Modulation of DNA Methyltransferases by S-Nitrosylation

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DESCRIPTION (provided by applicant): The focus of this research project is to study the effects of S-nitrosylation on the enzymatic activities of the mammalian DNA methyltransferases. Alterations in DNA methylation patterns are among the earliest and most common changes observed in cancer. Moreover, in many cancers such as liver, esophageal, gastric, colorectal, and bladder, chronic inflammation has been shown to play a causative role in carcinogenesis. Immune cells in inflammatory lesions produce significant amounts of microbicidal oxidants such as nitric oxide and superoxide that can have profound unintended effects on somatic cells, leading to carcinogenesis. The hypothesis to be explored in this project is that nitric oxide mediated S-nitrosylation of DNA methyltransferase enzymes modulates their activities in a manner that can alter DNA methylation patterns to promote carcinogenesis.