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DNMT

Three DNA methyltransferases (DNMTs), DNMT1, DNMT3a and DNMT3b, catalyze the transfer of a methyl group from S-adenosyl-L-methionine (SAM or AdoMet) to the C5 position of cytosine. DNMT1 is responsible for methylating hemimethylated DNA and thus DNA methylation maintenance, whereas DNMT3a and DNMT3b are involved in de novo DNA methylation, but they can also participate in methylation maintenance. DNMT3a has two different isoforms, and DNMT3b has more than 30 isoforms.  DNA methylation profile can be altered leading to DNA instability and triggering diseases such as cancer. In tumorigenesis, methylation in the promoter regions of some genes—such as tumor suppressor genes (TSGs) involved in cellular cycle (e.g., cyclin-dependent kinase (CDK) inhibitors, retinoblastoma protein (RB)), maintenance of genome integrity (e.g., TP53, breast cancer 1 (BRCA1), O6-methylguanine DNA methyltransferase (06-MGMT), mutL homolog 1 (hMLH1)), apoptosis (e.g., caspase 8, death-associated protein kinase (DAPK), migration process (e.g., E-cadherin (CDH1), metalloproteinase inhibitor 3 (TIMP-3)), and those involved in the response to growth factors (phosphatase and tensin homolog (PTEN), estrogen receptor (ER)) leads to their silencing.

References

1.Omar Castillo-Aguilera,et al. Biomolecules. 2017 Mar; 7(1): 3.