Reversal of nucleobase methylation by dioxygenases.

Guo-Liang Xu, Matthias Bochtler

Journal: Nature chemical biology 2020;16(11):1160-1169

PMID: 33067602

Full Text on Nature Publishing Group View on PubMed

Abstract

The repertoire of nucleobase methylation in DNA and RNA, introduced by chemical agents or enzymes, is large. Most methylation can be reversed either directly by restoration of the original nucleobase or indirectly by replacement of the methylated nucleobase with an unmodified nucleobase. In many direct and indirect demethylation reactions, ALKBH (AlkB homolog) and TET (ten eleven translocation) hydroxylases play a role. Here, we suggest a chemical classification of methylation types. We then discuss pathways for removal, emphasizing oxidation reactions. We highlight the recently expanded repertoire of ALKBH- and TET-catalyzed reactions and describe the discovery of a TET-like protein that resembles the hydroxylases but uses an alternative co-factor and catalyzes glyceryl transfer rather than hydroxylation.

Address: Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Medical College of Fudan University & Chinese Academy of Medical Sciences, Shanghai, China. [email protected].; State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China. [email protected].; International Institute of Molecular and Cell Biology, Warsaw, Poland. [email protected].; Polish Academy of Sciences, Institute of Biochemistry and Biophysics, Warsaw, Poland. [email protected].

DOI: 10.1038/s41589-020-00675-5