CHAPTER 8: Deamination of C-containing Cyclobutane Pyrimidine Dimers and Its Role in C to T and CC to TT Signature Mutations Caused by UV Light

Exposure of DNA to ultraviolet (UV) light produces cyclobutane pyrimidine dimers (CPDs) that have been linked to C to T and CC to TT signature mutations observed in skin cancers. The Cs or 5-methyCs (^mC) in CPD photoproducts formed from TC/^mC, CT and CC/^mC sites are not stable at neutral pH and can deaminate to the corresponding U/T-containing photoproduct. The deamination half-life of a C in a CPD can vary from a few hours to hundreds of hours depending on the dipyrimidine site, the flanking sequence, and its interaction with proteins and enzymes. Deamination of C/^mC in a CPD to U/T also changes the coding properties from C to T when bypassed by prokaryotic Pol V, or eukaryotic polymerase eta, the polymerases adapted to synthesize past CPDs. Deamination of C/^mC to U/T in CPDs is therefore predicted to be the major pathway for C/^mC to T mutations in both prokaryotes and eukaryotes, which is likely to be attenuated by the more rapid nucleotide excision repair of the deaminated CPDs due to the formation of a DNA-destabilizing mismatch.