DNA methyltransferase 1 (DNMT1) primarily methylates hemimethylated CpG sites on DNA following replication and has a key role in regulating gene expression. Previous work had identified the DNMT1 protein domains that recognize unmethylated DNA and prevent DNA methylation. This study reveals a complementary mechanism that governs the specificity of DNMT1 for hemimethylated DNA. The authors determined the crystal structure of mouse DNMT1 in complex with DNA containing a hemimethylated CpG site on the parental strand. They observed that hemimethylated DNA is recognized by the target recognition domain (TRD) within the methyltransferase domain, which forms a shallow concave surface that harbours the 5-methyl group of methylcytosine from the parental DNA strand. Biochemical analysis indicated that the hydrophobic environment generated by the residues lining the concave surface probably also has a role in determining substrate specificity.
ORIGINAL RESEARCH PAPER
Song, J. et al. Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation. Science 335, 709–712 (2012) Article
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David, R. DNMT1 learns to be picky. Nat Rev Mol Cell Biol 13, 139 (2012). https://doi.org/10.1038/nrm3301
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DOI: https://doi.org/10.1038/nrm3301