Role of DNA polymerase eta in the bypass of a (6-4) TT photoproduct

Mol Cell Biol. 2001 May;21(10):3558-63. doi: 10.1128/MCB.21.10.3558-3563.2001.


UV light-induced DNA lesions block the normal replication machinery. Eukaryotic cells possess DNA polymerase eta (Poleta), which has the ability to replicate past a cis-syn thymine-thymine (TT) dimer efficiently and accurately, and mutations in human Poleta result in the cancer-prone syndrome, the variant form of xeroderma pigmentosum. Here, we test Poleta for its ability to bypass a (6-4) TT lesion which distorts the DNA helix to a much greater extent than a cis-syn TT dimer. Opposite the 3' T of a (6-4) TT photoproduct, both yeast and human Poleta preferentially insert a G residue, but they are unable to extend from the inserted nucleotide. DNA Polzeta, essential for UV induced mutagenesis, efficiently extends from the G residue inserted opposite the 3' T of the (6-4) TT lesion by Poleta, and Polzeta inserts the correct nucleotide A opposite the 5' T of the lesion. Thus, the efficient bypass of the (6-4) TT photoproduct is achieved by the combined action of Poleta and Polzeta, wherein Poleta inserts a nucleotide opposite the 3' T of the lesion and Polzeta extends from it. These biochemical observations are in concert with genetic studies in yeast indicating that mutations occur predominantly at the 3' T of the (6-4) TT photoproduct and that these mutations frequently exhibit a 3' T-->C change that would result from the insertion of a G opposite the 3' T of the (6-4) TT lesion.

Publication types

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

MeSH terms

  • Animals
  • DNA / genetics
  • DNA / radiation effects
  • DNA Repair*
  • DNA-Directed DNA Polymerase / genetics*
  • Pyrimidine Dimers / genetics*
  • Saccharomyces cerevisiae / genetics
  • Ultraviolet Rays


  • Pyrimidine Dimers
  • DNA
  • DNA polymerase zeta
  • DNA-Directed DNA Polymerase