CHAPTER 11: Covalent Modifications of Nucleic Acids and Their Repair^†

The main DNA repair processes in humans involve direct repair (DR), base excision repair (BER), nucleotide excision repair (NER), interstrand crosslink repair (ICR) and base mismatch repair (BMR), as have been described in other chapters, in addition to homologous recombination (HR) and non-homologous end-joining (NHEJ). Studies on human repair systems have advanced rapidly, especially into UV damage, and recent studies have shown that human DNA polymerase η (Pol η) modulates susceptibility to skin cancer by promoting DNA synthesis past sunlight-induced cyclobutane pyrimidine dimers that have escaped nucleotide excision repair (NER). This bypass has low fidelity, meaning that in normal people, and especially in individuals with xeroderma pigmentosum who accumulate photodimers because they are NER-defective, the errors made by Pol η during dimer bypass may contribute to mutagenesis and to skin cancer. The depth of understanding that is now being achieved on the covalent modification of nucleic acids is awesome, both for adventitious (exogenous) and evolutionarily evolved (endogenous) modification. It is uncovering new questions and posing new challenges. A clear manifestation of this is the range of targets that have now been explored using cutting-edge methodologies that were unimaginable in earlier years. Above all, the advances made have brought us face-to-face with the amazing complexity of repair systems for our nucleic acids that supremely have made viable life on our planet.