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

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::

• cancer
• cell proliferation
• cellular plasticity
• DNA methylation
• DNA repair
• DNMT1
• non-catalytic activity
• pluripotency

Author contributions

The content of the manuscript was conceived, organized and written by the author.

Acknowledgments

Conceptualization of this manuscript was due to research work and discussions involving multiple former and present members of the author’s laboratory which was supported by Department of Biotechnology, Department of Science and Technology and Scientific Engineering Research Board and Indian Council of Medical Research. The author is grateful for the financial support from BITS Pilani under the Seed Grant, OPERA and Centre for Human Disease Research Programmes. The author thanks T Jamma, A Anne and S Choudhury for commenting on the draft versions of the manuscript.

Financial&competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The author has no relevant affiliations or financial involvement with anyorganization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending,or royalties.