Human CtIP promotes DNA end resection
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In the S and G2 phases of the cell cycle, DNA double-strand breaks (DSBs) are processed into single-stranded DNA, triggering ATR-dependent checkpoint signalling and DSB repair by homologous recombination. Previous work has implicated the MRE11 complex in such DSB-processing events. Here, we show that the human CtIP (RBBP8) protein confers resistance to DSB-inducing agents and is recruited to DSBs exclusively in the S and G2 cell-cycle phases. Moreover, we reveal that CtIP is required for DSB resection, and thereby for recruitment of replication protein A (RPA) and the protein kinase ATR to DSBs, and for the ensuing ATR activation. Furthermore, we establish that CtIP physically and functionally interacts with the MRE11 complex, and that both CtIP and MRE11 are required for efficient homologous recombination. Finally, we reveal that CtIP has sequence homology with Sae2, which is involved in MRE11-dependent DSB processing in yeast. These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination.
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End processing of double-strand breaks in homologous recombination contributes to DDR pathways.
“DSB end processing in HR also contributes to DDR pathways.”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [220]
CtIP is required for double-strand break end resection, recruitment of RPA and ATR to double-strand breaks, and subsequent ATR activation.
“CtIP is required for DSB end resection, the recruitment of RPA and ATR to DSBs, and subsequent ATR activation [98, 220]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [220]
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A nervous predisposition to unrepaired DNA double strand breaks
Reynolds, J. J., & Stewart, G. S. (2013) · DNA Repair · doi:10.1016/j.dnarep.2013.04.011 · Cited by 26 · see citing works
Molecular insights into the activation of Mre11-Rad50 endonuclease activity by Sae2/CtIP
Nicolas, Y., Bret, H., Cannavo, E., Acharya, A., Cejka, P., Borde, V., & Guerois, R. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.05.019 · Cited by 12 · see citing works
- Authors
- Sartori, A. A., Lukas, C., Coates, J., Mistrik, M., Fu, S., Bartek, J., Baer, R., Lukas, J., & Jackson, S. P.
- Affiliations
- University of Cambridge (GB)
- Danish Cancer Society (DK)
- Columbia University (US)
- Corresponding author
- Jackson, Stephen P.
- Venue
- Nature
- Published
- 2007-10-28
- Volume
- 450
- Issue
- 7169
- Pages
- 509-514
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2409435
- OpenAlex
- W1979385111
- Cited by
- 1,362
- References
- 50
- Citations by year
- 2026: 21 · 2025: 49 · 2024: 49 · 2023: 45 · 2022: 48 · 2021: 82 · 2020: 80 · 2019: 70 · 2018: 82 · 2017: 77 · 2016: 66 · 2015: 100 · 2014: 95 · 2013: 95 · 2012: 89
- FWCI
- 30.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Cancer Research UK (A5290)
- National Cancer Institute (P01CA097403)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- CtIP, RBBP8, DNA end resection, DNA double-strand breaks, Mre11 complex, homologous recombination, replication protein A, Sae2, DNA repair, single-stranded DNA, nuclease activity
- MeSH terms
- MRE11 Homologue Protein, Carrier Proteins, DNA, DNA Repair, DNA-Binding Proteins, DNA, Single-Stranded, Endodeoxyribonucleases, Endonucleases, Humans, Nuclear Proteins, Recombination, Genetic, G2 Phase, S Phase, Conserved Sequence, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Evolution, Molecular, Saccharomyces cerevisiae Proteins, Cell Line, Tumor, DNA Breaks, Double-Stranded, Ataxia Telangiectasia Mutated Proteins
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