Auto-methylation of the mouse DNA-(cytosine C5)-methyltransferase Dnmt3a at its active site cysteine residue

Siddique, Abu Nasar, Jurkowska, Renata Z. ORCID: https://orcid.org/0000-0002-4507-2222, Jurkowski, Tomasz P. ORCID: https://orcid.org/0000-0002-2012-0240 and Jeltsch, Albert 2011. Auto-methylation of the mouse DNA-(cytosine C5)-methyltransferase Dnmt3a at its active site cysteine residue. FEBS Journal 278 (12) , 2055—2063. 10.1111/j.1742-4658.2011.08121.x

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Abstract

The Dnmt3a DNA methyltransferase is responsible for establishing DNA methylation patterns during mammalian development. We show here that the mouse Dnmt3a DNA methyltransferase is able to transfer the methyl group from S‐adenosyl‐l‐methionine (AdoMet) to a cysteine residue in its catalytic center. This reaction is irreversible and relatively slow. The yield of auto‐methylation is increased by addition of Dnmt3L, which functions as a stimulator of Dnmt3a and enhances its AdoMet binding. Auto‐methylation was observed in binary Dnmt3a AdoMet complexes. In the presence of CpG containing dsDNA, which is the natural substrate for Dnmt3a, the transfer of the methyl group from AdoMet to the flipped target base was preferred and auto‐methylation was not detected. Therefore, this reaction might constitute a regulatory mechanism which could inactivate unused DNA methyltransferases in the cell, or it could simply be an aberrant side reaction caused by the high methyl group transfer potential of AdoMet.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Biosciences
Publisher:	Wiley: FEBS Journal
ISSN:	1742-464X
Date of Acceptance:	6 April 2011
Last Modified:	25 Oct 2022 13:09
URI:	https://orca.cardiff.ac.uk/id/eprint/119006

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