Figure 1.

Physiological and pathological roles of AID/APOBEC enzymes. In the genome, cytosine can be found in various forms: unmodified (C), methylated (mC), or oxidized mC bases (hmC, fC, and caC). The canonical function of AID/APOBECs in both innate and adaptive immunity is deamination of unmodified cytosine to uracil (dark gray). Mutational signatures in cancer have implicated AID/APOBEC activity on the human genome, on unmodified cytosine or possibly on mC (white). Alternative physiological roles for APOBECs have also been proposed (light gray), including in active DNA demethylation. These proposed pathways involve deamination of modified cytosine bases to their corresponding uracil analogs, followed by base excision repair to revert the original base to an unmodified cytosine.