DNMT1 transfers a methyl group from S-adenosylmethionine to the 5-position of the cytosine ring of cytosine residues in DNA. Purified human DNMT1 shows a 7 to 21-fold preference for hemimethylated CG motifs in DNA compared to unmethylated CG motifs (Pradhan et al. 1999) thus DNMT1 tends to maintain existing methylation through DNA replication. The binding of the CXXC motif of DNMT1 to cytosine in symmetrically unmethylated CG dinucleotides prevents access of cytosine to the active site and thereby prevents de novo methylation (Song et al. 2011). UHRF1 binds hemimethylated DNA and histone H3 tails methylated at lysine-9 and recruits DNMT1 to methylate hemimethylated DNA (Bostick et al. 2007, reviewed in Ooi and Bestor 2008). Interaction of UHRF1 with DNMT1 increases the methylation activity of DNMT1 about 5-fold (Bashtrykov et al. 2014).