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.