Reversal of nucleobase methylation by dioxygenases

Nat Chem Biol. 2020 Nov;16(11):1160-1169. doi: 10.1038/s41589-020-00675-5. Epub 2020 Oct 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AlkB Homolog 1, Histone H2a Dioxygenase / chemistry
  • Amino Acid Sequence
  • Binding Sites
  • Catalysis
  • DNA / chemistry*
  • DNA-Binding Proteins / chemistry*
  • Dioxygenases / metabolism*
  • Gene Expression Regulation
  • Glycosides / chemistry
  • Humans
  • Hydroxylation
  • Methylation
  • Mixed Function Oxygenases / metabolism
  • Oxidation-Reduction
  • Protein Conformation
  • RNA / chemistry*
  • SOX9 Transcription Factor / chemistry
  • Signal Transduction

Substances

  • DNA-Binding Proteins
  • Glycosides
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • RNA
  • DNA
  • Mixed Function Oxygenases
  • Dioxygenases
  • AlkB Homolog 1, Histone H2a Dioxygenase