Translesion DNA Synthesis

Human DNA polymerase η (pol η) is the gene product that is altered in the variant form of xeroderma pigmentosum. Pol η has a structure that can accommodate the cyclobutane pyrimidine dimer, the most prominent ultraviolet-induced DNA lesion. Pol η catalyzes efficient and accurate translesion DNA synthesis (TLS) under the fine control of systems involving interactions with mono-ubiquitinated proliferating cell nuclear antigen. Pol η can also catalyze TLS past cisplatin lesions, which might contribute to the resistance of tumors to chemotherapy. Other Y-family polymerases, pol ι, pol κ, and REV1, and a B-family polymerase pol ζ can contribute to erroneous TLS past ultraviolet-induced lesions. However, these polymerases also contribute to the maintenance of genomic stability in the presence of their cognate DNA lesions. A-family polymerases, pol θ and pol ν, also have TLS abilities, and pol θ has an important role in an alternative end-joining repair pathway for DNA double-strand breaks, protecting against genomic instability. PrimPol is a protein with DNA polymerase and primase activities that is capable of initiating de novo DNA/RNA synthesis and that also has the capacity to bypass modifications that stall the replisome, by TLS or origin-independent re-priming. This chapter summarizes our current knowledge relating to DNA polymerases that are capable of catalyzing TLS.