Non-catalytic functions of DNMT1.

Mammalian DNA methyltransferase 1 (DNMT1) is essential during early embryo development. Consistent with its key role in embryogenesis, depletion of this protein in adult somatic cells promotes severe cellular dysfunctions and cell death. DNMT1 contains a highly evolutionary conserved C-terminal catalytic DNA methyltransferase domain that is thought to be the responsible for the maintenance of CpG methylation patterns in the genome. DNMT1 has also a large N-terminal region with different functional protein-protein and protein-DNA binding domains. The multi-domain N-terminal region and the abundant molecular binding patterns suggest potential non-catalytic functions for DNMT1. However, this hypothesis remains controversial and conflicting results can be found in the literature. Here, recent results presenting a functional role for DNMT1 independent of its catalytic domain are discussed.