Methylation-Demethylation Dynamics: Implications of Changes in Acute Kidney Injury

Figure 3

Mechanism of active DNA demethylation. The active process of DNA demethylation progresses either through the deamination or the oxidation pathway. In the case of the deamination pathway, the cytosine (C) residue of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) undergoes deamination catalysed by AID/APOBEC enzymes to generate 5-hydroxymethyluracil (5hmU) and thymine (T) bases which are replaced by C during base excision repair (BER) mediated by thymine DNA glycosylase (TDG). The oxidation pathway mediated by the ten-eleven translocation (TET) family of enzymes can hydroxylate 5mC to form 5hmC which upon oxidation forms 5fC and 5caC. These oxidation products (5fC and 5caC) can be removed by TDG to generate an abasic site which is repaired by the BER pathway to generate a cytosine.