DNA methyltransferase 1 and 3A (DNMT1/3A)

DNA methyltransferase 1 (DNMT1) and DNA methyltransferase 3A (DNMT3A) are essential enzymes that regulate the epigenetic landscape of the human genome by catalyzing the addition of methyl groups to cytosine residues in DNA [1, 12]. DNMT1 serves as the primary maintenance methyltransferase, ensuring that established methylation patterns are faithfully inherited by daughter cells during DNA replication, while DNMT3A acts as a de novo methyltransferase responsible for creating new methylation marks during development and cellular differentiation [7, 14]. In various malignancies, particularly hematological cancers like acute myeloid leukemia (AML), these enzymes are often overexpressed or mutated, leading to the pathological silencing of tumor suppressor genes through promoter hypermethylation [9, 15]. Therapeutic strategies targeting DNMT1 and DNMT3A utilize hypomethylating agents, such as azacitidine and decitabine, to inhibit enzymatic activity and restore normal gene expression, thereby inducing cell cycle arrest or apoptosis in cancer cells [8, 11]. However, because these enzymes are vital for normal cellular function and genomic integrity, pharmacological inhibition can lead to significant side effects, including myelosuppression and potential off-target toxicities in healthy tissues [13, 17].

Other names

DNA (cytosine-5)-methyltransferase 1DNA (cytosine-5)-methyltransferase 3ADNMT1DNMT3AMCMTDNA methyltransferase 1/3ADNA methyltransferase 1 and 3A complex

Inhibition of DNA methyltransferase activity through covalent trapping or competitive binding, leading to global and gene-specific DNA hypomethylation and the subsequent reactivation of silenced tumor suppressor genes.