Requirement of DNA polymerase η for error-free bypass of UV-induced CC and TC photoproducts

The yeast RAD30-encoded DNA polymerase eta (Pol eta) bypasses a cis-syn thymine-thymine dimer efficiently and accurately. Human DNA polymerase eta functions similarly in the bypass of this lesion, and mutations in human Pol eta result in the cancer prone syndrome, the variant form of xeroderma pigmentosum. UV light, however, also elicits the formation of cis-syn cyclobutane dimers and (6-4) photoproducts at 5'-CC-3' and 5'-TC-3' sites, and in both yeast and human DNA, W-induced mutations occur primarily by 3' C to T transitions. Genetic studies presented here reveal a role for yeast Pol eta in the error-free bypass of cyclobutane dimers and (6-4) photoproducts formed at CC and TC sites. Thus, by preventing UV mutagenesis at a,vide spectrum of dipyrimidine sites, Pol eta plays a pivotal role in minimizing the incidence of sunlight-induced skin cancers in humans.