DNMT1: catalytic and non-catalytic roles in different biological processes

Epigenomics. 2022 May;14(10):629-643. doi: 10.2217/epi-2022-0035. Epub 2022 Apr 12.

Abstract

DNMT1 is the main enzyme that uses the information on DNA methylation patterns in the parent strand and methylates the daughter strand in freshly replicated hemimethylated DNA. It is widely known that DNMT1 is a component of the epigenetic machinery mediating gene repression via increased promoter methylation. However, recent data suggest that DNMT1 can also modulate gene expression independent of its catalytic activity and participates in multiple processes including the cell cycle, DNA damage repair and stem cell function. This review summarizes the noncanonical functions of DNMT1, some of which are clearly independent of maintenance methylation. Finally, phenotypic data on altered DNMT1 levels suggesting that maintenance of optimal levels of DNMT1 is vital for normal development and health is presented.

Keywords: DNA methylation; DNA repair; DNMT1; cancer; cell proliferation; cellular plasticity; non-catalytic activity; pluripotency.

Publication types

  • Review

MeSH terms

  • Biological Phenomena*
  • DNA (Cytosine-5-)-Methyltransferase 1 / genetics
  • DNA (Cytosine-5-)-Methyltransferase 1 / metabolism
  • DNA (Cytosine-5-)-Methyltransferases* / genetics
  • DNA (Cytosine-5-)-Methyltransferases* / metabolism
  • DNA / metabolism
  • DNA Methylation
  • Humans
  • Promoter Regions, Genetic

Substances

  • DNA
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases