Specificity of Dnmt1 for methylation of hemimethylated CpG sites resides in its catalytic domain

Bashtrykov, Pavel, Jankevicius, Gytis, Smarandache, Anita, Jurkowska, Renata Z. ORCID: https://orcid.org/0000-0002-4507-2222, Ragozin, Sergey and Jeltsch, Albert 2012. Specificity of Dnmt1 for methylation of hemimethylated CpG sites resides in its catalytic domain. Chemistry and Biology 19 (5) , pp. 572-578. 10.1016/j.chembiol.2012.03.010

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Abstract

The maintenance methylation of hemimethylated CpG sites by the DNA methyltransferase Dnmt1 is the molecular basis of the inheritance of DNA methylation patterns. Based on structural data and kinetics obtained with a truncated form of Dnmt1, an autoinhibition model for the specificity of Dnmt1 was proposed in which unmethylated DNA binds to Dnmt1's CXXC domain, which prevents its methylation. We have prepared CXXC domain variants that lost DNA binding. Corresponding full-length Dnmt1 variants did not display a reduction in specificity, indicating that the autoinhibition model does not apply in full-length Dnmt1. Furthermore, we show that the Dnmt1 M1235S variant, which carries an exchange in the catalytic domain of the enzyme, has a marked reduction in specificity, indicating that the recognition of the hemimethylated state of target sites resides within the catalytic domain.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Elsevier (Cell Press)
ISSN:	1074-5521
Date of Acceptance:	21 March 2012
Last Modified:	09 Nov 2022 10:22
URI:	https://orca.cardiff.ac.uk/id/eprint/139284

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