DNA (cytosine-5)-methyltransferase 1 (DNMT1) (DNMT1)

DNA (cytosine-5)-methyltransferase 1 (DNMT1) is a critical enzyme responsible for maintaining DNA methylation patterns across cell generations by recognizing hemi-methylated CpG sites during DNA replication (UniProt P26358). It plays a fundamental role in epigenetic regulation, gene silencing, and genomic stability (NIH Gene ID: 1786). In many cancers, particularly hematological malignancies, DNMT1 is often overexpressed, leading to the hypermethylation and silencing of tumor suppressor genes (PMID: 22830447). Decitabine, a cytidine analog, serves as a potent inhibitor of DNMT1; upon incorporation into DNA, it covalently traps the enzyme, triggering its degradation and subsequent global DNA hypomethylation (PubChem CID: 451669). This therapeutic approach aims to restore the expression of silenced genes to induce cell differentiation or apoptosis in malignant cells (StatPearls: Decitabine).

Other names

DNA methyltransferase 1MCMTCXXC-type zinc finger protein 9CXXC9HSN1EADCADN

Decitabine acts as a hypomethylating agent by incorporating into DNA during replication and forming a covalent bond with DNMT1, which traps the enzyme and leads to its proteasomal degradation, resulting in global DNA hypomethylation and reactivation of silenced genes.