Impact of ribonucleotide incorporation by DNA polymerases β and λ on oxidative base excision repair
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Nature communications - 7(2016) vom: 26. Feb., Seite 10805 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Crespan, Emmanuele [VerfasserIn] |
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| Links: |
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| Themen: |
5Z93L87A1R |
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| Anmerkungen: |
Date Completed 12.07.2016 Date Revised 09.12.2020 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/ncomms10805 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM257861807 |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Bertoletti, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Mentegari, Elisa |e verfasserin |4 aut | |
| 700 | 1 | |a Chiapparini, Giulia |e verfasserin |4 aut | |
| 700 | 1 | |a Imhof, Ralph |e verfasserin |4 aut | |
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| 700 | 1 | |a Sturla, Shana J |e verfasserin |4 aut | |
| 700 | 1 | |a Hübscher, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a van Loon, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Maga, Giovanni |e verfasserin |4 aut | |
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