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Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation
Open accessAbstract
Claspin is a homolog of Mrc1, a checkpoint protein required for the DNA replication checkpoint in yeast. In Xenopus , phosphorylated Claspin binds to xChk1 and regulates xChk1 activation in response to replication stress. In this study, we have shown that the human homolog of Claspin is required for resistance to multiple forms of genotoxic stress including UV, IR, and hydroxyurea. Phosphorylation of Claspin was found to depend on the ataxia telangiectasia mutated-Rad3 related (ATR) pathway. DNA damage induces the formation of a complex between Claspin and BRCA1, a second regulator of Chk1 activation. Claspin was found to control BRCA1 phosphorylation on serine 1524, a site whose phosphorylation is controlled by the ATR pathway. These results are consistent with a model in which ATR regulates Claspin phosphorylation in response to DNA damage and replication stress resulting in recruitment and phosphorylation of BRCA1. BRCA1 and Claspin then function to activate the tumor suppressor Chk1. Unexpectedly, we found that Claspin has a second, positive role in control of the cell cycle as Claspin overexpression increased cell proliferation. These results suggest that Claspin has properties of both a tumor suppressor and an oncogene.
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“Claspin, a Chk1-binding protein, is required for ATR-Chk1 checkpoint activation [127–129].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [129]
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Cites
Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
Zou, L., & Elledge, S. J. (2003) · Science · doi:10.1126/science.1083430 · Cited by 2,693
Self-citationCell cycle checkpoint signaling through the ATM and ATR kinases
Abraham, R. T. (2001) · Genes & Development · doi:10.1101/gad.914401 · Cited by 1,966
Liu, Q., Guntuku, S., Cui, X.-S., Matsuoka, S., Cortez, D., Tamai, K., Luo, G., Carattini-Rivera, S., DeMayo, F., Bradley, A., et al. (2000) · Genes & Development · doi:10.1101/gad.14.12.1448 · Cited by 1,625
Self-citationLinkage of ATM to Cell Cycle Regulation by the Chk2 Protein Kinase
Matsuoka, S. (1998) · Science · doi:10.1126/science.282.5395.1893 · Cited by 1,322
Sanchez, Y., Wong, C., Thoma, R. S., Richman, R., Wu, Z., Piwnica-Worms, H., & Elledge, S. J. (1997) · Science · doi:10.1126/science.277.5331.1497 · Cited by 1,320
Self-citationAtaxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro
Matsuoka, S., Rotman, G., Ogawa, A., Shiloh, Y., Tamai, K., & Elledge, S. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190030497 · Cited by 849
Self-citationRadiosensitivity in ataxia-telangiectasia: a new explanation.
Painter, R. B., & Young, B. R. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.12.7315 · Cited by 795
O'Driscoll, M., Ruiz-Perez, V. L., Woods, C. G., Jeggo, P. A., & Goodship, J. A. (2003) · Nature Genetics · doi:10.1038/ng1129 · Cited by 794
S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex
Katou, Y., Kanoh, Y., Bando, M., Noguchi, H., Tanaka, H., Ashikari, T., Sugimoto, K., & Shirahige, K. (2003) · Nature · doi:10.1038/nature01900 · Cited by 649
ATM and ATR: networking cellular responses to DNA damage
Shiloh, Y. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00159-3 · Cited by 601
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Brondello, J., Ducommun, B., Fernandez, A., & Lamb, N. J. C. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.01.091 · Cited by 16
New insights into genetic instability of an industrial CHO cell line by orthogonal omics
Qian, Y., Sowa, S. W., Aron, K. L., Xu, P., Langsdorf, E. F., Warrack, B. M., Aranı́bar, N., Tremml, G., Xu, J., McVey, D., et al. (2020) · Biochemical Engineering Journal · doi:10.1016/j.bej.2020.107799 · Cited by 15
Lee, E.-M., Trinh, T. T. B., Shim, H. J., Park, S.-K., Nguyen, T. T. T., Kim, M., & Song, Y. (2012) · DNA repair · doi:10.1016/j.dnarep.2012.06.007 · Cited by 15
Checkpoint Regulation of DNA Replication
Boye, E., Skjølberg, H. C., & Grallert, B. (2009) · Methods in molecular biology · doi:10.1007/978-1-60327-815-7_4 · Cited by 17
Claspin is phosphorylated in the Chk1-binding domain by a kinase distinct from Chk1
Bennett, L. N., Larkin, C., Gillespie, D. A., & Clarke, P. R. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.02.154 · Cited by 14
Hammond-Martel, I., Pak, H., Yu, H., Rouget, R., Horwitz, A. A., Parvin, J. D., Drobetsky, E. A., & Affar, E. B. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014027 · Cited by 13
Cantor, S. B., & Nayak, S. U. (2016) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2016.02.003 · Cited by 13
Claspin: From replication stress and DNA damage responses to cancer therapy
Azenha, D., Lopes, M. C., & Martins, T. (2018) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2018.10.007 · Cited by 13
Interactions of HIV‐1 Viral Protein R with Host Cell Proteins
Zhao, Y., Elder, R. T., & Bukrinsky, M. (2007) · Advances in pharmacology · doi:10.1016/s1054-3589(07)55007-6 · Cited by 12
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2023) · Biological Procedures Online · doi:10.1186/s12575-023-00201-6 · Cited by 11
Suominen, M. I., Knuuttila, M., Schatz, C. A., Schlicker, A., Vääräniemi, J. P., Sjöholm, B., Alhoniemi, E. J., Haendler, B., Mumberg, D., Käkönen, S.-M., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032189 · Cited by 9
TOPBP1 , CLSPN and PALB2 genes in familial breast cancer susceptibility
Erkko, H. (2008) · Cited by 9
Targeting the Cdc2‐like kinase 2 for overcoming platinum resistance in ovarian cancer
Jiang, Y., Huang, S., Zhang, L., Zhou, Y., Zhang, W., Wan, T., Gu, H., Ouyang, Y., Zheng, X., Liu, P., et al. (2024) · MedComm · doi:10.1002/mco2.537 · Cited by 8
DNA Damage: Placing BRCA1 in the Proper Context
Aressy, B., & Greenberg, R. A. (2012) · Current Biology · doi:10.1016/j.cub.2012.07.046 · Cited by 7
Feu, S., Unzueta, F., Llopis, A., Semple, J. I., Ercilla, A., Guaita‐Esteruelas, S., Jaumot, M., Freire, R., & Agell, N. (2020) · The FASEB Journal · doi:10.1096/fj.201901926r · Cited by 7
Guerra, B., Doktor, T. K., Frederiksen, S. B., Somyajit, K., & Andresen, B. S. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04374-3 · Cited by 7
Drf1-dependent Kinase Interacts with Claspin through a Conserved Protein Motif
Gold, D. A., & Dunphy, W. G. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.077370 · Cited by 7
Madgwick, S., Luli, S., Sellier, H., Butterworth, J. A., Leslie, J., Moore, A. J., Corbin, E. K., Yemm, A. I., Chiremba, R. T., TINIAKOS, D. G., et al. (2022) · Biochemical Journal · doi:10.1042/bcj20220101 · Cited by 6
Sahay, O., Barik, G. K., Sharma, T., Pillai, A. D., Rapole, S., & Santra, M. K. (2021) · DNA repair · doi:10.1016/j.dnarep.2021.103261 · Cited by 4
Single-Stranded DNA Binding Proteins Involved in Genome Maintenance
Richard, D. J., & Khanna, K. K. (2009) · Springer eBooks · doi:10.1007/978-90-481-2561-6_16 · Cited by 4
Fischer, I., Cunliffe, C. H., Bollo, R. J., Weiner, H. L., Devinsky, O., Tachiquín, M. E. R., Venuto, T., Pearlman, A. W., Chiriboga, L. A., Schneider, R. J., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0391-1 · Cited by 4
Regulation of checkpoint kinase signalling and tumorigenesis by the NF-κB regulated gene, CLSPNPreprint
Hunter, J. E., Butterworth, J. A., Sellier, H., Luli, S., Floudas, A., Moore, A. J., Thomas, H. D., Campbell, K. J., Kenneth, N. S., Chiremba, R. T., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/358291 · Cited by 4
Chen, Y., Li, Y., Liang, Z., Yang, Z., Ren, H., Wei, W., Niu, Y., & Shang, Z. (2025) · iScience · doi:10.1016/j.isci.2025.113520 · Cited by 3
Functional relationship between Claspin and Rad17
Yoshimura, A., Akita, M., Hosono, Y., Abe, T., Kobayashi, M., Yamamoto, K.-I., Tada, S., Seki, M., & Enomoto, T. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.09.037 · Cited by 3
Towards finding the complete modulome: density constrained biclustering
Çolak, R. (2008) · Summit (Simon Fraser University) · Cited by 3
Claspin and Cancer: Where Are We Now?
Azenha, D., & Martins, T. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26188828 · Cited by 2
Claspin is involved in S-phase checkpoint induced by benzo(a)pyrene in 16HBE cells
Qi, Y., Zhao, P., Fu, J., Yao, B., Yuan, Z., Hu, E., & Zhou, Z. (2009) · Toxicology in Vitro · doi:10.1016/j.tiv.2009.05.006 · Cited by 2
Elbasateeny, S. S., Abdelwahab, M. M., Mahmoud, A. A., Malek, M. M., Yassin, M. A., Ismail, A. M., & Ibrahim, H. (2022) · The Egyptian Journal of Hospital Medicine · doi:10.21608/ejhm.2022.270276 · Cited by 1
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Lin, S., Dai, H., & Elledge, S. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.19.660578 · Cited by 1
Self-citationThe phosphoproteomic landscape of the DNA damage responsePreprint
Conte, F., Ostermaier, M., Wang, J., Goss, C., Sayols, S., Chen, J.-X., Roukos, V., Graeter, F., Aponte-Santamaria, C. A., Luck, K., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.11.724232 · Cited by 1
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Oakes, V. (2012)
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Toh, Y. K. (2009) · ERA
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Chen, C. (2014) · DukeSpace (Duke University)
Signaling at Stalled Replication Forks
Mordes, D. A., & Cortez, D. (2009) · Springer eBooks · doi:10.1007/978-90-481-2561-6_2
Gold, D. A. (2009) · CaltechTHESIS (California Institute of Technology) · doi:10.7907/xg90-5475
McAndrew, C. W., Gastwirt, R. F., & Donoghue, D. J. (2008) · Wiley eBooks · doi:10.1002/9780470048672.wecb057
Selective targeting of cancer cells through inhibition of Checkpoint kinase 1
Hasvold, G. (2012) · NORA - Norwegian Open Research Archives
RAD9A Stabilization and Destabilization Processes in Checkpoint Maintenance and Checkpoint Recovery
Zambrano, O., & Frend, W. H. C. (2015) · QSpace (Queen's University Library)
Interactions of Claspin with replication and checkpoint proteins
Serçin, Ö. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/ae0r-t506
Chen, Y., Pereira, E., & Sánchez, Y. (2007) · AfCS-Nature Molecule Pages · doi:10.1038/mp.a000642.01
(2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2517068122
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26593757
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26593763
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26593781
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26593787
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26593784
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26593760
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26593778
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26593769
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26593772
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26593766
Chen, Y., Wen, H., Li, Y., Han, Y., Tan, J., Guo, C., Cai, C., Liu, P., Peng, Y., Liu, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26593775
Bianco, J. N. (2010) · theses.fr (ABES) · doi:10.70675/c5c5f7fbz5b45z423ezbc8azeb8ce3450ec3
Role of CTF18 and SAMHD1 in human DNA replication and genome integrity maintenance
Silva, M. J. (2014) · theses.fr (ABES) · doi:10.70675/988b3c5fzb231z4dbfz989cz8f4343b71a76
Impact of low replication stress on the replication program of cancer and non-tumor cells
Courtot, L. (2020) · theses.fr (ABES) · doi:10.70675/74d8bf42zeebdz4323zb869zec66e6e29157
Metadata
- Authors
- Lin, S.-Y., Li, K., Stewart, G. S., & Elledge, S. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-04-19
- Volume
- 101
- Issue
- 17
- Pages
- 6484-6489
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC404071
- OpenAlex
- W2129258256
- Cited by
- 156
- References
- 27
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 11 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 8 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 3 · 2012: 7
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Cancer Institute (F32CA093043)
- National Institute of General Medical Sciences (GM-44664, R37GM044664, R01GM044664)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- Claspin, BRCA1, Chk1, ATR pathway, DNA damage response, genotoxic stress resistance, replication stress, cell proliferation, tumor suppressor, oncogenes, protein phosphorylation, hydroxyurea
- MeSH terms
- Base Sequence, Carrier Proteins, Cell Division, Cell Survival, DNA Damage, Humans, Oligoribonucleotides, Phosphorylation, Protein Binding, BRCA1 Protein, Xenopus Proteins, Adaptor Proteins, Signal Transducing
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