Oxidative demethylation of DNA and RNA mediated by non-heme iron-dependent dioxygenases.

Overview

DNA/RNA methylation can be generated by methyltransferases and thus plays a critical role in regulating cellular processes; alternatively, nucleic acid methylation can be produced by methylation agents and is cytotoxic/mutagenic if left unrepaired. Oxidative demethylation mediated by non-heme iron-dependent dioxygenases is an efficient way to reverse either the cellular roles of regulatory methylation or the cytotoxic/mutagenic effects of methylation damage. In this Focus Review we summarize recent advances in the study of nucleic acid dioxygenases exemplified by the TET and AlkB family proteins, with an emphasis on chemical insights from the recent literature. Comparison of the chemical mechanisms of these dioxygenases revealed that differences in the mechanism also contribute significantly to their distinct biological functions.