DNMT1

By Jamshed Arslan Pharm.D.

Epigenetics is the process of heritable change in gene activity despite alteration of the hosts DNA sequence, essentially causing a change in a phenotype without a change in the genotype of a host. To change the gene sequence without interfering with the DNA is accomplished by histone and DNA methylation.  Gene silencing in DNA methylation is carried out by DNA methyltransferases 1, 2 and 3a/b (DNMT1, DNMT2, DNMT3A/B). On a broad level, DNMT’s methylate the fifth carbon of cytosine residues in DNA within CG dinucleotides.

Epigenetics is the study of heritable change in gene activity despite alteration of the hosts DNA sequence.  Change in gene activity done independently of the DNA sequence is achieved by way of histone and DNA methylation.  Gene silencing in DNA methylation is carried out by DNA methyltransferases 1, 2 and 3a/b (DNMT1, DNMT2, DNMT3A/B). On a broad level, DNMTs methylate the fifth carbon of cytosine residues in DNA within CG dinucleotides.

Dnmt1 belongs to the C5-methyltransferase family that repairs cytosines in dsDNA using a nucleophilic attack mechanism. Dnmt1 is the most abundant mammalian DNA methyltransferase. It is the key methylation maintenance enzyme for both DNA replication/repair and de novo methylation during somatic cell development and differentiation.

Proliferating Cell Nuclear Antigen (PCNA), also known as the polymerase delta auxiliary protein, is a nuclear protein essential for DNA replication as well as DNA excision and mismatch repair pathways. It has a large role in cell cycle regulation and response of cells to stress.

DNA methyltransferases catalyze the transfer of the methyl group from S-andenosyl methionine (SAM) to DNA. Such methylation has wide ranging function in the cell, including organismal development and cell differentiation. In cancer, abnormal hypermethylation of gene promoter CpG islands can result in transcriptional silencing.