DNA methyltransferase 1 (DNMT1) (DNMT1)

DNA methyltransferase 1 (DNMT1) is a critical enzyme responsible for the maintenance of DNA methylation patterns, ensuring the faithful transmission of epigenetic information during cell division [UniProt]. It specifically recognizes hemi-methylated CpG sites on the daughter strand of DNA and catalyzes the transfer of a methyl group from S-adenosyl-L-methionine [NCBI Gene]. In various cancers, particularly hematologic malignancies like myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), DNMT1 is often overexpressed, leading to the silencing of tumor suppressor genes through promoter hypermethylation [PubMed]. Therapeutic inhibition of DNMT1 is achieved using hypomethylating agents such as azacitidine and decitabine, which act as nucleoside analogs that incorporate into DNA and trap the enzyme in a covalent complex, triggering its degradation [DrugBank]. While azacitidine also incorporates into RNA, the primary clinical efficacy in treating myeloid disorders is linked to the depletion of DNMT1 and the subsequent restoration of gene expression [StatPearls]. The inclusion of "DNA & RNA" in the target name likely reflects the dual nucleic acid incorporation of certain inhibitors, although DNMT1's catalytic activity is specific to DNA [Nature Communications].

Other names

DNA (cytosine-5)-methyltransferase 1MCMTDNMTCXXC9DNA methyltransferase HsaI

Covalent trapping and subsequent proteasomal degradation of the DNMT1 enzyme following the incorporation of nucleoside analog inhibitors into the DNA strand [DrugBank].