Twists and turns of DNA methylation
DNA methylation, the postreplicative transfer of a methyl group to the C5 position of cytosine bases, was the first epigenetic modification identified and has been intensively studied for more than half a century. By now it is clear that Dnmt1, the major eukaryotic DNA methyltransferase, faithfully maintains genome-wide methylation patterns and plays an essential role in the epigenetic network controlling gene expression and genome stability during development. However, the molecular mechanisms that ultimately control DNA methylation still remain elusive. This is, in part, attributable to the remarkable complexity of the DNA methylation reaction, the apparent involvement of several inter- and intramolecular protein interactions, and the limited structural information. The crystal structure of Dnmt1 presented in PNAS (1) now provides detailed insights into the inner workings and possible regulation of one of the most intriguing enzymes.