DNA methyltransferase 1 and DNA methyltransferase 3 beta (DNMT1 and DNMT3B)

DNA methyltransferase 1 (DNMT1) and DNA methyltransferase 3 beta (DNMT3B) are essential enzymes that catalyze the transfer of methyl groups to cytosine residues in DNA, a process fundamental to epigenetic regulation and gene silencing (Frontiers in Genetics, 2018; J Clin Med, 2025). DNMT1 is primarily responsible for maintaining established methylation patterns during DNA replication, ensuring epigenetic inheritance across cell divisions, whereas DNMT3B acts as a de novo methyltransferase that establishes new methylation marks during early embryonic development (NIH, 2025; Frontiers in Oncology, 2020). In various malignancies, including acute myeloid leukemia and solid tumors, the overexpression or aberrant recruitment of these enzymes leads to the hypermethylation of CpG islands in the promoters of tumor suppressor genes, effectively silencing them and promoting oncogenesis (NIH, 2017; ResearchGate, 2024). Therapeutic strategies targeting DNMT1 and DNMT3B involve hypomethylating agents, such as the nucleoside analogs azacitidine and decitabine, which incorporate into DNA and irreversibly trap the enzymes, leading to their degradation and the restoration of normal gene expression (Patsnap, 2024; SCBT, 2024). Beyond cancer, mutations in DNMT3B are the primary cause of ICF syndrome, while DNMT1 mutations are associated with specific neurodegenerative disorders like HSAN1E, highlighting their critical roles in human health and development (Patsnap, 2025; Creative Biolabs, 2024).

Other names

DNA (cytosine-5)-methyltransferase 1DNA (cytosine-5)-methyltransferase 3 betaMCMTDNMTCXXC9HSN1EICFICF1M.HsaIIIB

Hypomethylating agents like azacitidine and decitabine act as nucleoside analogs that incorporate into DNA during the S-phase, where they form irreversible covalent bonds with DNMT enzymes, leading to their proteasomal degradation and subsequent global DNA hypomethylation.