Structure-Based Mechanistic Insights into DNMT1-Mediated Maintenance DNA Methylation

Abstract

Close-Up of DNA Methylation In eukaryotes, maintenance of genomic CpG methylation patterns is required for imprinting, retrotransposon silencing, and X-chromosome inactivation. The epigenetic mark needs to be faithfully maintained and propagated during repeated cell divisions in somatic cells by selective methylation of hemimethylated CpG dinucleotides following DNA replication, which is carried out by the enzyme DNMT1. Song et al. (p. 709 ) determined the crystal structure of mouse DNMT1 bound to a DNA duplex containing a hemimethylated CpG on the parental strand, such as would be found immediately after DNA replication. Together with a previous structure of the autoinhibited structure, the findings suggest that a combination of active and auto-inhibitory mechanisms ensures the high fidelity of DNMT1-mediated maintenance of DNA methylation.