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

E. Crespan,A. Furrer,M. Rösinger,F. Bertoletti,Elisa Mentegari,Giulia Chiapparini,Ralph Imhof,Nathalie Ziegler,S. Sturla,U. Hübscher,B. van Loon,G. Maga

Published 2016 in Nature Communications

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. Oxidative stress is a common source of DNA damage and is repaired by the base excision repair machinery, including polymerase beta. Here the authors find that polymerase beta, and to a lesser extent lambda, can mistakenly incorporate ribonucleotides during synthesis.

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