DNA lesions in the template strand pose a block to the replication machinery. Replication across such lesions may occur by a mutagenic bypass process in which a wrong base is inserted opposite the lesion or may involve processes that are relatively error-free. Genetic studies in the yeast Saccharomyces cerevisiae have indicated the requirement of REV3-encoded DNA polymerase in mutagenic bypass. The DNA polymerase responsible for error- free bypass, however, has not been identified, but genetic studies implicating proliferating cell nuclear antigen in this process have suggested that either DNA polymerase δ or DNA polymerase ε may be involved. Here, we use temperature-sensitive (ts) conditional lethal mutations of the S. cerevisiae POL2 and POL3 genes, which encode DNA polymerase ε and δ, respectively, and show that post-replicational bypass of UV-damaged DNA is severely inhibited in the pol3-3 mutant at the restrictive temperature. By contrast, the pol2-18 mutation has no adverse effect on this process at the restrictive temperature. From these observations, we infer a requirement of DNA polymerase δ in post-replicative bypass of UV-damaged DNA.
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