The checkpoint clamp, Rad9-Rad1-Hus1 complex, preferentially stimulates the activity of apurinic/apyrimidinic endonuclease 1 and DNA polymerase in long patch base excision repair
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Growing evidence suggests that the Rad9-Rad1-Hus1 complex (the 9-1-1 complex), besides its functions in DNA damage sensing and signaling pathways, plays also a direct role in various DNA repair processes. Recent studies have demonstrated that the 9-1-1 complex physically and functionally interacts with several components of the base excision repair (BER) machinery namely DNA polymerase beta (Pol beta), flap endonuclease 1 (Fen 1), DNA ligase I (Lig I) and the MutY homologue of Schizosaccharomyces pombe. In this work, we found for the first time that the 9-1-1 complex interacts in vitro and in vivo with the apurinic/apyrimidinic endonuclease 1 (APE 1), an early component of BER, and can stimulate its AP-endonuclease activity. Moreover, we show that the 9-1-1 complex possesses a stimulatory effect on long patch base excision repair (LP-BER) reconstituted in vitro. The enhancement of LP-BER activity is due to the specific stimulation of the two early components of the repair machinery, namely APE 1 and Pol beta, suggesting a hierarchy of interactions between the 9-1-1 complex and the BER proteins acting in the repairosome. Overall, our results indicate that the 9-1-1 complex is directly involved in LP-BER, thus providing a possible link between DNA damage checkpoints and BER.
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The 9-1-1 complex interacts with BER proteins APE1, Pol β, FEN1, DNA ligase I, and DNA glycosylases MutY, NEIL1, and TDG, stimulating their DNA repair activities.
“As a critical component of ATR-Chk1 checkpoint pathway, the 9-1-1 complex interacts with several BER proteins: APE1, Polymerase β (Pol β), FEN1, DNA ligase I, as well as DNA glycosylases MutY, NEIL1, and TDG, thereby stimulating their DNA repair activities [177–185] (Fig. 3).”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [184]
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- Authors
- Gembka, A., Toueille, M., Smirnova, E., Poltz, R., Ferrari, E., Villani, G., & Hubscher, U.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-03-29
- Volume
- 35
- Issue
- 8
- Pages
- 2596-2608
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC1885638
- OpenAlex
- W2007991116
- Cited by
- 74
- References
- 61
- Citations by year
- 2026: 3 · 2024: 1 · 2022: 6 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 10 · 2014: 1 · 2013: 12 · 2012: 6
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (190312)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- long-patch base excision repair, apurinic/apyrimidinic endonuclease 1, DNA polymerase beta, DNA repair, DNA damage checkpoint, protein-protein interaction
- MeSH terms
- DNA Ligase ATP, Cell Line, DNA, DNA Repair, Enzyme Activation, Exonucleases, Humans, DNA Ligases, Cell Cycle Proteins, DNA Polymerase beta, DNA-(Apurinic or Apyrimidinic Site) Lyase, Flap Endonucleases
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