title: Impact of ribonucleotide incorporation by DNA polymerases β and λ on oxidative base excision repair.
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.
authors.affiliation: DNA Enzymology &Molecular Virology Unit, Institute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: Emmanuele
authors.initials: E
authors.lastname: Crespan
authors.affiliation: Department of Molecular Mechanisms of Disease, University of Zürich, CH-8057 Zürich, Switzerland.
authors.forename: Antonia
authors.initials: A
authors.lastname: Furrer
authors.affiliation: Department of Molecular Mechanisms of Disease, University of Zürich, CH-8057 Zürich, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Rösinger
authors.affiliation: DNA Enzymology &Molecular Virology Unit, Institute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Bertoletti
authors.affiliation: DNA Enzymology &Molecular Virology Unit, Institute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Mentegari
authors.affiliation: DNA Enzymology &Molecular Virology Unit, Institute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Chiapparini
authors.affiliation: Department of Molecular Mechanisms of Disease, University of Zürich, CH-8057 Zürich, Switzerland.
authors.forename: Ralph
authors.initials: R
authors.lastname: Imhof
authors.affiliation: Department of Health Sciences and Technology, ETH Zurich, CH-8092 Zürich, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ziegler
authors.affiliation: Department of Health Sciences and Technology, ETH Zurich, CH-8092 Zürich, Switzerland.
authors.forename: Shana J
authors.initials: SJ
authors.lastname: Sturla
authors.affiliation: Department of Molecular Mechanisms of Disease, University of Zürich, CH-8057 Zürich, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hübscher
authors.affiliation: Department of Molecular Mechanisms of Disease, University of Zürich, CH-8057 Zürich, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: van Loon
authors.affiliation: DNA Enzymology &Molecular Virology Unit, Institute of Molecular Genetics IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: Giovanni
authors.identifier: http://orcid.org/0000-0001-8092-1552
authors.initials: G
authors.lastname: Maga
mesh_terms: D000818:Animals; D002460:Cell Line; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism*; D019951:DNA Polymerase beta / Q000378:metabolism*; D004260:DNA Repair; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D051379:Mice; D018384:Oxidative Stress; D012265:Ribonucleotides / Q000378:metabolism*
chemical_list: C453560:7,8-dihydro-8-oxoguanine; D012265:Ribonucleotides; D006147:Guanine; C415367:DNA polymerase beta2; D019951:DNA Polymerase beta; D045647:DNA Glycosylases