Lesion bypass by S. cerevisiae Pol ζ alone

Jana E. Stone, Dinesh Kumar, Sara K. Binz, Aki Inase, Shigenori Iwai, Andrei Chabes, Peter M. Burgers, Thomas A. Kunkel

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

DNA polymerase zeta (Pol ζ) participates in translesion synthesis (TLS) of DNA adducts that stall replication fork progression. Previous studies have led to the suggestion that the primary role of Pol ζ in TLS is to extend primers created when another DNA polymerase inserts nucleotides opposite lesions. Here we test the non-exclusive possibility that Pol ζ can sometimes perform TLS in the absence of any other polymerase. To do so, we quantified the efficiency with which S. cerevisiae Pol ζ bypasses abasic sites, cis-syn cyclobutane pyrimidine dimers and (6-4) photoproducts. In reactions containing dNTP concentrations that mimic those induced by DNA damage, a Pol ζ derivative with phenylalanine substituted for leucine 979 at the polymerase active site bypasses all three lesions at efficiencies between 27 and 73%. Wild-type Pol ζ also bypasses these lesions, with efficiencies that are lower and depend on the sequence context in which the lesion resides. The results are consistent with the hypothesis that, in addition to extending aberrant termini created by other DNA polymerases, Pol ζ has the potential to be the sole DNA polymerase involved in TLS.

Original languageEnglish
Pages (from-to)826-834
Number of pages9
JournalDNA Repair
Volume10
Issue number8
DOIs
StatePublished - Aug 15 2011

Keywords

  • Abasic sites.
  • DNA polymerase zeta
  • Translesion synthesis
  • UV photoproducts

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