DNA methyl transferase 1: regulatory mechanisms and implications in health and disease

International Journal of Biochemistry and Molecular Biology

Sirano Dhe-Paganon¹  Farisa Syeda¹  Lawrence Park¹ 

关键词: DNMT1;    catalytic regulation;    epigenetics;    disease implications;   

DOI  :  

学科分类：生物化学/生物物理

来源: e-Century Publishing Corporation

【 摘 要 】

DNA methylation serves as the principal form of post-replicative epigenetic modification. It is intricately involved in gene regulation and silencing in eukaryotic cells, making significant contributions to cell phenotype. Much of it is mitotically inherited; some is passed on from one filial generation to the next. Establishment and maintenance of DNA methylation patterns in mammals is governed by three catalytically active DNA methyltransferases – DNMT3a, DNMT3b and DNMT1. While the first two are responsible mainly for de novo methylation, DNMT1 maintains the methylation patterns by preferentially catalyzing S-adenosyl methionine-dependant transfer of a methyl group to cytosine at hemimethylated CpG sites generated as a result of semi-conservative DNA replication. DNMT1 contains numerous regulatory domains that fine-tune associated catalytic activities, deregulation of which is observed in several diseases including cancer. In this minireview, we analyze the regulatory mechanisms of various sub-domains of DNMT1 protein and briefly discuss its pathophysiological and pharmacological implications. A better understanding of DNMT1 function and structure will likely reveal new applications in the treatment of associated diseases.

【 授权许可】

Unknown