DNMT1

DNMT1 (DNA methyltransferase 1) is the principal maintenance DNA methyltransferase that preferentially recognizes hemimethylated CpG sites and preserves DNA methylation patterns during DNA replication, thereby supporting epigenetic inheritance and stable gene regulation^[1][2]. Mechanistically, DNMT1 functions within the DNA methylation machinery that maintains chromatin states, transcriptional programs, and genome stability, and its recruitment to newly replicated DNA is coordinated by factors such as UHRF1^[3][4]. Through maintenance of CpG methylation, DNMT1 contributes to developmental processes, cellular identity, and long-term repression of transposable elements^[1][5]. In disease contexts, aberrant DNMT1 activity is strongly associated with cancer, where sustained DNA methylation can promote silencing of tumor-suppressor genes and support malignant phenotypes^[1][6][7]. Experimental studies further demonstrate that selective depletion of DNMT1 induces global and gene-specific demethylation and reactivates silenced tumor-suppressor genes in human cancer cells, highlighting its central role in epigenetic regulation^[7]. Compared with the related de novo methyltransferases DNMT3A and DNMT3B, which establish new methylation patterns, DNMT1 primarily propagates existing methylation marks after DNA replication, although recent evidence indicates that DNMT1 can also exhibit context-dependent de novo methylation activity, particularly at retrotransposon loci^[5][8]. For experimental applications, DNMT1 remains a major epigenetic drug target, and both nucleoside-based and emerging selective non-nucleoside inhibitors are widely used to investigate DNA methylation dynamics and therapeutic reprogramming of aberrant epigenetic states^[6][9].