DNMT1
DNMT1 (DNA methyltransferase 1) is the enzyme that copies DNA methylation patterns from the parent strand to the daughter strand after each replication, making it the carrier of epigenetic inheritance through cell division.
Function
DNA methylation at CpG dinucleotides is the genome’s long-term regulatory memory: promoters of silent genes are methylated, promoters of active genes are generally unmethylated. DNMT1 has a preference for hemimethylated CpG sites — the state of every CpG immediately after replication — and methylates the new strand to match the old. The protein is recruited to the replication fork by PCNA and UHRF1, which recognizes hemimethylation. Maintenance methylation is how a liver cell’s daughters remain liver cells; without it, methylation patterns would halve with every division.
In cancer
Cancer genomes show two methylation failures at once: global hypomethylation (which destabilizes chromosomes and reactivates transposable elements) and focal hypermethylation of CpG islands at tumor suppressor promoters, silencing genes such as CDKN2A and MLH1 without any DNA sequence change. DNMT1 is overexpressed in many tumors, and DNMT inhibitors (azacitidine, decitabine) are approved for myelodysplastic syndromes.
Notes
- Human gene symbol: DNMT1; UniProt P26358; 1,616 amino acids; DMAP1-binding, replication-foci targeting, and BAH domains.