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Impact of ribonucleotide incorporation by DNA polymerases β and λ on oxidative base excision repair

Author

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  • Emmanuele Crespan

    (DNA Enzymology & Molecular Virology Unit, Institute of Molecular Genetics IGM-CNR)

  • Antonia Furrer

    (University of Zürich)

  • Marcel Rösinger

    (University of Zürich)

  • Federica Bertoletti

    (DNA Enzymology & Molecular Virology Unit, Institute of Molecular Genetics IGM-CNR)

  • Elisa Mentegari

    (DNA Enzymology & Molecular Virology Unit, Institute of Molecular Genetics IGM-CNR)

  • Giulia Chiapparini

    (DNA Enzymology & Molecular Virology Unit, Institute of Molecular Genetics IGM-CNR)

  • Ralph Imhof

    (University of Zürich)

  • Nathalie Ziegler

    (ETH Zurich)

  • Shana J. Sturla

    (ETH Zurich)

  • Ulrich Hübscher

    (University of Zürich
    Present address: Department of Chemistry and Biology, Konstanz Research School Chemical Biology, University of Konstanz, Universitätsstrasse 10, 78457 Konstanz, Germany (U.H.))

  • Barbara van Loon

    (University of Zürich)

  • Giovanni Maga

    (DNA Enzymology & Molecular Virology Unit, Institute of Molecular Genetics IGM-CNR)

Abstract

Oxidative stress is a very frequent source of DNA damage. Many cellular DNA polymerases (Pols) can incorporate ribonucleotides (rNMPs) during DNA synthesis. However, whether oxidative stress-triggered DNA repair synthesis contributes to genomic rNMPs incorporation is so far not fully understood. Human specialized Pols β and λ are the important enzymes involved in the oxidative stress tolerance, acting both in base excision repair and in translesion synthesis past the very frequent oxidative lesion 7,8-dihydro-8-oxoguanine (8-oxo-G). We found that Pol β, to a greater extent than Pol λ can incorporate rNMPs opposite normal bases or 8-oxo-G, and with a different fidelity. Further, the incorporation of rNMPs opposite 8-oxo-G delays repair by DNA glycosylases. Studies in Pol β- and λ-deficient cell extracts suggest that Pol β levels can greatly affect rNMP incorporation opposite oxidative DNA lesions.

Suggested Citation

  • Emmanuele Crespan & Antonia Furrer & Marcel Rösinger & Federica Bertoletti & Elisa Mentegari & Giulia Chiapparini & Ralph Imhof & Nathalie Ziegler & Shana J. Sturla & Ulrich Hübscher & Barbara van Loo, 2016. "Impact of ribonucleotide incorporation by DNA polymerases β and λ on oxidative base excision repair," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10805
    DOI: 10.1038/ncomms10805
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