DNA methyltransferase 1 and DNA methyltransferase 3 alpha (DNMT1 and DNMT3A)

DNA methyltransferase 1 (DNMT1) and DNA methyltransferase 3 alpha (DNMT3A) are critical enzymes responsible for establishing and maintaining DNA methylation patterns across the genome. DNMT1 is primarily known as the maintenance methyltransferase, ensuring that epigenetic marks are copied from parent to daughter strands during DNA replication, while DNMT3A functions as a de novo methyltransferase that establishes new methylation patterns during development and cellular differentiation (Source: UniProt P26358, Q9Y6K1). In many cancers, these enzymes are often overexpressed or mutated, leading to the hypermethylation of tumor suppressor gene promoters and subsequent gene silencing, which promotes oncogenesis and tumor progression (Source: NIH, National Cancer Institute). Therapeutic targeting of these enzymes typically involves nucleoside analogs like azacitidine and decitabine, which incorporate into DNA and irreversibly bind the enzymes, triggering their degradation and restoring normal gene expression patterns. Beyond oncology, mutations in DNMT3A are frequently observed in clonal hematopoiesis and are associated with an increased risk of hematologic malignancies and cardiovascular disease (Source: PubMed, PMID: 25426838).

Other names

DNA (cytosine-5)-methyltransferase 1DNA (cytosine-5)-methyltransferase 3 alphaMCMTDNMTDNA MTaseDNA methyltransferase 3A

DNA methyltransferase inhibitors (DNMTis) act as nucleoside analogs that incorporate into DNA during replication. Once incorporated, they covalently trap DNMT enzymes (DNMT1, DNMT3A, and DNMT3B) onto the DNA, leading to the depletion of active enzymes and subsequent global DNA hypomethylation, which can reactivate silenced tumor suppressor genes (Source: PubMed, PMID: 25735915).