Specificity of DNA lesion bypass by the yeast DNA polymerase eta

J Biol Chem. 2000 Mar 17;275(11):8233-9. doi: 10.1074/jbc.275.11.8233.


DNA polymerase eta (Pol(eta), 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 thymine-thymine cis-syn-cyclobutane dimer. We have purified the yeast Pol(eta) and studied its lesion bypass activity in vitro with various types of DNA damage. The yeast Pol(eta) 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 approximately 100:56:14, respectively. The yeast Pol(eta) 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 Pol(zeta) following the Pol(eta) action opposite an AP site, achieving true lesion bypass. In contrast, the yeast Pol(alpha) 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, Pol(eta) may also play a role in bypassing additional DNA lesions, some of which can be error-prone.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Acetylaminofluorene / analogs & derivatives
  • 2-Acetylaminofluorene / metabolism
  • Apurinic Acid / metabolism
  • DNA Damage*
  • DNA Replication*
  • DNA, Fungal / biosynthesis*
  • DNA-Directed DNA Polymerase / metabolism*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Guanine / analogs & derivatives
  • Guanine / metabolism
  • Polynucleotides / metabolism
  • Pyrimidine Dimers / metabolism
  • Saccharomyces cerevisiae / genetics*


  • DNA, Fungal
  • Polynucleotides
  • Pyrimidine Dimers
  • apyrimidinic acid
  • Apurinic Acid
  • N-(deoxyguanosin-8-yl)acetylaminofluorene
  • 8-hydroxyguanine
  • Guanine
  • 2-Acetylaminofluorene
  • DNA polymerase iota
  • DNA-Directed DNA Polymerase
  • Rad30 protein
  • Deoxyguanosine