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Lesion bypass by S. cerevisiae Pol ζ alone
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2011 (English)In: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 10, no 8, 826-834 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2011. Vol. 10, no 8, 826-834 p.
Keyword [en]
DNA polymerase zeta, Translesion synthesis, UV photoproducts, Abasic sites
National Category
Medical Genetics Pharmacology and Toxicology
URN: urn:nbn:se:umu:diva-58137DOI: 10.1016/j.dnarep.2011.04.032ISI: 000294033800005PubMedID: 21622032OAI: diva2:547022
Available from: 2012-08-26 Created: 2012-08-26 Last updated: 2015-11-03Bibliographically approved

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Kumar, DineshChabes, Andrei
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Molecular Infection Medicine Sweden (MIMS)Department of Medical Biochemistry and Biophysics
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