Figure 4.
Mechanism of DNA cytosine C5 methylation. (A) The DNA methylation reaction catalyzed by DNA methyltransferase (DNMT). (B) Resonance structures of cytosine showing that C5 is not nucleophilic due to the presence of the carbonyl at C2. Resonance structure 3 is more stable than 2, which is more stable than 1. (C) Nucleophilic attack by a Cys residue in DNMT convert cytosine to a nucleophile, which then undergoes methylation in an SN2 type reaction. Elimination of the Cys residue gives the methylated cytosine residue.