Specificity of DNA lesion bypass by the yeast DNA polymerase η

DNA polymerase η (Polη, xeroderma pigmentosum variant, or Rad30) plays an important role in an error-free response to unrepaired UV damage during replication. It faithfully synthesizes DNA opposite a thyminethymine cis-syn- cyclobutane dimer. We have purified the yeast Polη and studied its lesion bypass activity in vitro with various types of DNA damage. The yeast Polη lacked a nuclease or a proofreading activity. It efficiently bypassed 8- oxoguanine, incorporating C, A, and G opposite the lesion with a relative efficiency of ~100: 56:14, respectively. The yeast Polη efficiently incorporated a C opposite an acetylaminofluorene-modified G, and efficiently inserted a G or less frequently an A opposite an apurinic/apyrimidinic (AP) site but was unable to extend the DNA synthesis further in both cases. However, some continued DNA synthesis was observed in the presence of the yeast Polζ following the Polη action opposite an AP site, achieving true lesion bypass. In contrast, the yeast Polα was able to bypass efficiently a template AP site, predominantly incorporating an A residue opposite the lesion. These results suggest that other than UV damage, Polη may also play a role in bypassing additional DNA lesions, some of which can be error-prone.