Spontaneous deamination is the hydrolysis reaction of cytosine into uracil, releasing ammonia in the process. This can occur in vitro through the use of bisulfite, which deaminates cytosine, but not 5-methylcytosine. This property has allowed researchers to sequence methylated DNA to distinguish non-methylated cytosine (shown up as uracil) and methylated cytosine (unaltered).
In DNA, this spontaneous deamination is corrected for by the removal of uracil (product of cytosine deamination and not part of DNA) by uracil-DNA glycosylase, generating an abasic (AP) site. The resulting abasic site is then recognised by enzymes (AP endonucleases) that break a phosphodiester bond in the DNA, permitting the repair of the resulting lesion by replacement with another cytosine. A DNA polymerase may perform this replacement via nick translation, a terminal excision reaction by its 5⟶3 exonuclease activity, followed by a fill-in reaction by its polymerase activity. DNA ligase then forms a phosphodiester bond to seal the resulting nicked duplex product, which now includes a new, correct cytosine (Base excision repair).