Figure 4.

Modification of 5-methylcytosine leads to the restoration of unmethylated cytosine. 5-mC is oxidized by TET protein to 5-hmC, 5-formylcytosine (5-fc), and 5-carboxylcytosine (5caC). Thymine (T) can also be oxidized by TET to 5-Hydroxyuracil (5-hmU). Deamination of 5-mC and 5-hmC by an enzyme complex Activation-induced deaminase/apolipoprotein B mRNA-editing catalytic polypeptide-like (ADI/APOBEC) leads to the formation of thymine and 5-hmU. The final step in restoring cytosine occurs with Base Excision Repair (BER) and thymine DNA glycosylase (TDG), which modify 5-fc, 5-caC, 5-hmU, and T [76,77,78,79,80].