DNA methyltransferase (DNMT) (DNMT)

DNA methyltransferases (DNMTs) are a family of enzymes, including DNMT1, DNMT3A, and DNMT3B, that catalyze the transfer of a methyl group to the C5 position of cytosine residues in DNA (UniProt P26358). This epigenetic modification is a fundamental mechanism for gene silencing, genomic imprinting, and maintaining chromosomal stability (PubMed: 20418874). In many cancers, particularly hematological malignancies like Myelodysplastic Syndromes (MDS), aberrant DNMT activity leads to hypermethylation of tumor suppressor gene promoters, contributing to oncogenesis (StatPearls: NBK537112). Drugs targeting these enzymes, such as the nucleoside analogs azacitidine and decitabine, act as suicide substrates that incorporate into the DNA during replication. Once incorporated, they form stable covalent complexes with DNMTs, leading to enzyme depletion and subsequent global DNA hypomethylation (PubChem CID 451669). This process facilitates the re-expression of silenced genes and can induce cell cycle arrest or apoptosis in malignant cells.

Other names

DNA (cytosine-5)-methyltransferaseDNMT1DNMT3ADNMT3BCytosine-5 methyltransferaseDNA methyltransferases via DNA incorporation

Covalent inhibition and depletion of DNA methyltransferases following their entrapment by drug-incorporated DNA strands.