Fig. 1

DNA methylation/demethylation mechanics. a Methyl groups (green circles) are transferred to C in order to generate 5-mC. DNA methyltransferases (DNMT) catalyze this process. In the “active DNA demethylation” the TET DNA demethylase converts 5-mC to 5-hmC, which is further processed to 5-fC and 5-caC. These residues are targets for the DNA repair pathway, whose most critical component is the hTDG, which is responsible also for the repair of U:G and T:G mismatches. DNA demethylation can also occur through spontaneous cytosine deamination, which is catalyzed by AID/APOBEC enzymes. This gives rise to 5-hmU and T bases. Transient U:G and T:G mismatches can be repaired by the TDG/BER pathway. b De novo and maintenance methylation occur using unmethylated DNA and hemimethylated/post-replication DNA as templates for DNMT enzymes. In the absence of maintenance methylation, progressive dilution of 5-mC or its oxidized derivatives at DNA replication can determine the appearance of unmethylated DNA. This process is known as “passive DNA demethylation”