title: Lesion bypass by S. cerevisiae Pol ζ alone.
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.
authors.affiliation: Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.
authors.forename: Jana E
authors.initials: JE
authors.lastname: Stone
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.forename: Sara K
authors.initials: SK
authors.lastname: Binz
authors.forename: Aki
authors.initials: A
authors.lastname: Inase
authors.forename: Shigenori
authors.initials: S
authors.lastname: Iwai
authors.forename: Andrei
authors.initials: A
authors.lastname: Chabes
authors.forename: Peter M
authors.initials: PM
authors.lastname: Burgers
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kunkel
mesh_terms: D001080:Apurinic Acid / Q000737:chemistry; D002453:Cell Cycle; D004249:DNA Damage; D017931:DNA Primers / Q000737:chemistry; D004271:DNA, Fungal / Q000096:biosynthesis; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics; D003854:Deoxyribonucleotides / Q000737:chemistry*; D020125:Mutation, Missense; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*
chemical_list: D017931:DNA Primers; D004271:DNA, Fungal; D003854:Deoxyribonucleotides; D029701:Saccharomyces cerevisiae Proteins; D001080:Apurinic Acid; C425929:DNA polymerase zeta; D004259:DNA-Directed DNA Polymerase