DNA methyltransferase 1 (DNMT1) is the primary enzyme responsible for preserving DNA methylation patterns after DNA replication. By preferentially recognizing hemi-methylated CpG sites, DNMT1 faithfully restores methylation on newly synthesized DNA strands, ensuring stable inheritance of epigenetic information. This activity is essential for embryonic development, genomic imprinting, X-chromosome inactivation, and long-term genome integrity.

Maintenance of DNA Methylation

During S phase, DNMT1 transfers methyl groups from S-adenosylmethionine (SAM) to unmethylated cytosines opposite methylated parental strands. Although mainly a maintenance methyltransferase, it can also mediate context-dependent de novo methylation at selected genomic loci, including transposable elements and imprint control regions.

Regulation and Biological Functions

• Protein interactions: DNMT1 cooperates with UHRF1 and PCNA to ensure accurate methylation inheritance during DNA replication.
• Epigenetic regulation: Its activity is controlled by post-translational modifications, including phosphorylation, acetylation, ubiquitination, and O-GlcNAcylation.
• Biological significance: DNMT1 regulates stem cell maintenance, neuronal development, genome stability, and transposable element silencing. Aberrant expression contributes to cancer, aging, and developmental disorders, making DNMT1 an important therapeutic target for epigenetic drugs such as azacitidine and decitabine.