mDNMT1 in complex with DNA

DNA methylation is essential for the regulation of chromatin structure and tissue-specific gene expression. It is associated with gene silencing and prevents aberrant protein expression, thus contributing to genome stability. In mammalian cells, non-de novo methylation is largely coordinated by DNA methyltransferase1 (DNMT1). DNMT1 has high preference for hemimethylated CpG dinucleotides (which occur after DNA replication) and transfers a methyl group to the unmethylated CpG cytosine, therefore maintaining genomic methylation patterns. Equally, non-excessive DNA methylation is also important for controlled gene expression. Aberrant hypermethylation results in the inactivation of important genes, such as the silencing of tumour suppressor genes which results in cancer cell proliferation. Therefore, both a specificity and (auto)inhibitory mechanism must be present. Here, we explore the autoinhibitory conformation of DNMT1. Let’s dissect this complex molecule and learn how controlled methylation is achieved!