Modulation of DNA Methyltransferases by S-Nitrosylation

描述(申请人提供)：本研究项目的重点是研究S亚硝化对哺乳动物DNA甲基转移酶酶活性的影响。DNA甲基化模式的变化是癌症中观察到的最早和最常见的变化之一。此外，在许多癌症中，如肝癌、食道癌、胃癌、结直肠癌和膀胱癌，慢性炎症已被证明在癌症发生中起到了致癌作用。炎症病变中的免疫细胞会产生大量的杀菌氧化剂，如一氧化氮和超氧化物，这些氧化剂可能对体细胞产生深远的意外影响，导致癌症发生。这个项目要探索的假设是，一氧化氮介导的脱氧核糖核酸甲基转移酶酶的S亚硝化可以调节它们的活性，从而改变脱氧核糖核酸甲基化模式，促进癌症的发生。

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.