DNMT1: Small Molecules and Peptides

DNMT1 (DNA methyltransferase 1; also MCMT and CXXC-type Zn finger protein 9) is a 190 kDa member of the C5-methyltransferase family of enzymes. DNMT1 is ubiquitous in expression, and appears during the S-phase of the cell cycle. DNMT1 catalyzes the attachment of a methyl group to the C5 position of CpG cytosines using AdoMet/adenosylmethionine as a co factor. This acts to silence select genes during X chromosome inactivation and tumorigenesis. Human DNMT1 is 1616 amino acids (aa) in length. DNMT1 contains an N-terminal regulatory, homodimerization and target recognition region (aa 1-1100), a Gly-Lys linker segment (aa 1109-1120) and a catalytic domain (aa 1121-1616). DNMT1 is acetylated, phosphorylated, and SUMOylated. There are multiple splice variants of DNMT1. There is a deletion of aa 1-336, alternative start sites at Met122 and 62 aa upstream of the standard start site, and a 17 aa substitution for Pro149. Over aa 1381-1587, human DNMT1 shares 87% aa identity with mouse DNMT1.