Figure 2.

Schematic representation of the methylation reaction catalyzed by the DNA methyltransferases (DNMTs) (adapted from [14]). Shown are the mechanisms proposed for methylation of cytosine by DNMT1, 3a and 3b on DNA (upper left panel) or by DNMT2 on RNA (lower left panel). Briefly, a thiol group (SH) from the binding site of the enzyme provides the nucleophilic attack to position 6 of the cytosine heterocycle, to activate position 5 towards one-carbon transfer (I). The methyl group on position 5 is donated by the coenzyme AdoMet (II). A proton in position 5 of the 5,6-dihydropyrimidine is then removed (II–III), and a consequent β-elimination generate 5-methylcitosyne and free enzyme (IV).