title: Dnmt1 structure and function.
abstract: Dnmt1, the principal DNA methyltransferase in mammalian cells, is a large and a highly dynamic enzyme with multiple regulatory features that can control DNA methylation in cells. This chapter highlights how insights into Dnmt1 structure and function can advance our understanding of DNA methylation in cells. The allosteric site(s) on Dnmt1 can regulate processes of de novo and maintenance DNA methylation in cells. Remaining open questions include which molecules, by what mechanism, bind at the allosteric site(s) in cells? Different phosphorylation sites on Dnmt1 can change its activity or ability to bind DNA target sites. Thirty-one different molecules are currently known to have physical and/or functional interaction with Dnmt1 in cells. The Dnmt1 structure and enzymatic mechanism offer unique insights into those interactions. The interacting molecules are involved in chromatin organization, DNA repair, cell cycle regulation, and apoptosis and also include RNA polymerase II, some RNA-binding proteins, and some specific Dnmt1-inhibitory RNA molecules. Combined insights from studies of different enzymatic features of Dnmt1 offer novel ideas for development of drug candidates, and can be used in selection of promising drug candidates from more than 15 different compounds that have been identified as possible inhibitors of DNA methylation in cells.
authors.affiliation: Medical Biochemistry, PB Rab, Faculty of Medicine, University of Rijeka, Rab, Croatia.
authors.forename: Željko M
authors.initials: ŽM
authors.lastname: Svedružić
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D051379:Mice; D013329:Structure-Activity Relationship
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse