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The absence of the catalytic domains of Saccharomyces cerevisiae DNA polymerase ϵ strongly reduces DNA replication fidelity
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2019 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 47, no 8, p. 3986-3995Article in journal (Refereed) Published
Abstract [en]

The four B-family DNA polymerases α, δ, ϵ and ζ cooperate to accurately replicate the eukaryotic nuclear genome. Here, we report that a Saccharomyces cerevisiae strain encoding the pol2-16 mutation that lacks Pol ϵ's polymerase and exonuclease activities has increased dNTP concentrations and an increased mutation rate at the CAN1 locus compared to wild type yeast. About half of this mutagenesis disappears upon deleting the REV3 gene encoding the catalytic subunit of Pol ζ. The remaining, still strong, mutator phenotype is synergistically elevated in an msh6Δ strain and has a mutation spectrum characteristic of mistakes made by Pol δ. The results support a model wherein slow-moving replication forks caused by the lack of Pol ϵ's catalytic domains result in greater involvement of mutagenic DNA synthesis by Pol ζ as well as diminished proofreading by Pol δ during replication.

Place, publisher, year, edition, pages
Oxford University Press, 2019. Vol. 47, no 8, p. 3986-3995
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-156351DOI: 10.1093/nar/gkz048ISI: 000473754300019PubMedID: 30698744OAI: oai:DiVA.org:umu-156351DiVA, id: diva2:1287880
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Swedish Cancer SocietySwedish Research CouncilAvailable from: 2019-02-12 Created: 2019-02-12 Last updated: 2019-07-25Bibliographically approved

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Sharma, SushmaChabes, Andrei

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