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

Emmanuele Crespan, Antonia Furrer, Marcel Rösinger, Federica Bertoletti, Elisa Mentegari, Giulia Chiapparini, Ralph Imhof, Nathalie Ziegler, Shana J. Sturla, Ulrich Hübscher, Barbara van Loon () and Giovanni Maga ()
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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
Barbara van Loon: University of Zürich
Giovanni Maga: DNA Enzymology & Molecular Virology Unit, Institute of Molecular Genetics IGM-CNR

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: 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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10805

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DOI: 10.1038/ncomms10805

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