The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Control of the DNA Damage Checkpoint by Chk1 and Rad53 Protein Kinases Through Distinct Mechanisms
Abstract
In response to DNA damage, cells activate checkpoint pathways that prevent cell cycle progression. In fission yeast and mammals, mitotic arrest in response to DNA damage requires inhibitory Cdk phosphorylation regulated by Chk1. This study indicates that Chk1 is required for function of the DNA damage checkpoint in Saccharomyces cerevisiae but acts through a distinct mechanism maintaining the abundance of Pds1, an anaphase inhibitor. Unlike other checkpoint mutants, chk1 mutants were only mildly sensitive to DNA damage, indicating that checkpoint functions besides cell cycle arrest influence damage sensitivity. Another kinase, Rad53, was required to both maintain active cyclin-dependent kinase 1, Cdk1(Cdc28), and prevent anaphase entry after checkpoint activation. Evidence suggests that Rad53 exerts its role in checkpoint control through regulation of the Polo kinase Cdc5. These results support a model in which Chk1 and Rad53 function in parallel through Pds1 and Cdc5, respectively, to prevent anaphase entry and mitotic exit after DNA damage. This model provides a possible explanation for the role of Cdc5 in DNA damage checkpoint adaptation.
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“In budding yeast, Mec1 activates both Rad53 and Chk1 [26], while in human cells Chk2 is activated by ATM and Chk1 by ATR [27].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [26]
Citations
Cites
Cell Cycle Checkpoints: Preventing an Identity Crisis
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The Phosphatase Cdc14 Triggers Mitotic Exit by Reversal of Cdk-Dependent Phosphorylation
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Ciosk, R., Zachariae, W., Michaelis, C., Shevchenko, A., Mann, M., & Nasmyth, K. (1998) · Cell · doi:10.1016/s0092-8674(00)81211-8 · Cited by 595
Regulation of RAD53 by the ATM -Like Kinases MEC1 and TEL1 in Yeast Cell Cycle Checkpoint Pathways
Sanchez, Y., Desany, B. A., Jones, W. J., Liu, Q., Wang, B., & Elledge, S. J. (1996) · Science · doi:10.1126/science.271.5247.357 · Cited by 585
Self-citationAllen, J. B., Zhou, Z. Y., Siede, W., Friedberg, E. C., & Elledge, S. J. (1994) · Genes & Development · doi:10.1101/gad.8.20.2401 · Cited by 497
Self-citationShirayama, M., Zachariae, W., Ciosk, R., & Nasmyth, K. (1998) · The EMBO Journal · doi:10.1093/emboj/17.5.1336 · Cited by 483
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Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathwayPreprint
Desany, B. A., Alcasabas, A. A., Bachant, J. B., & Elledge, S. J. (1998) · Genes & Development · doi:10.1101/gad.12.18.2956 · Cited by 448
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Research works printed but not linked: 1
- Supplementary material can be found at www.sciencemag.org/feature/data/1042771.shl
Cited by
Sorted by citations
The DNA damage response: putting checkpoints in perspective
Zhou, B.-B. S., & Elledge, S. J. (2000) · Nature · doi:10.1038/35044005 · Cited by 3,213
Self-citationLiu, 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-citationMitotic kinases as regulators of cell division and its checkpoints
Nigg, E. A. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35048096 · Cited by 1,541
ATR-Mediated Checkpoint Pathways Regulate Phosphorylation and Activation of Human Chk1
Zhao, H., & Piwnica-Worms, H. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.13.4129-4139.2001 · Cited by 1,091
Schultz, L. B., Chehab, N. H., Malikzay, A., & Halazonetis, T. D. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.7.1381 · Cited by 916
Metadata
- Authors
- Sanchez, Y., Bachant, J., Wang, H., Hu, F., Liu, D., Tetzlaff, M., & Elledge, S. J.
- Affiliations
- Howard Hughes Medical Institute,
- Howard Hughes Medical Institute (US)
- Corresponding author
- Bachant, Jeff
- Elledge, Stephen J.
- Venue
- Science
- Published
- 1999-11-05
- Volume
- 286
- Issue
- 5442
- Pages
- 1166-1171
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2091204939
- Cited by
- 536
- References
- 27
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 14 · 2023: 7 · 2022: 13 · 2021: 7 · 2020: 11 · 2019: 18 · 2018: 12 · 2017: 12 · 2016: 18 · 2015: 15 · 2014: 12 · 2013: 26 · 2012: 15
- FWCI
- 12.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM-44664)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- DNA damage checkpoint, Chk1, Rad53, Pds1, Cdc5, Polo kinase, CDK1, Cdc28, mitotic arrest, checkpoint adaptation, Saccharomyces cerevisiae, cell cycle regulation
- MeSH terms
- Checkpoint Kinase 1, Anaphase, DNA Damage, DNA, Fungal, Fungal Proteins, Ligases, Mitosis, Mutation, Nuclear Proteins, Phosphorylation, Protein Kinases, Recombinant Fusion Proteins, Saccharomyces cerevisiae, S Phase, CDC2 Protein Kinase, RNA-Binding Proteins, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Cyclin B, Saccharomyces cerevisiae Proteins, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Intracellular Signaling Peptides and Proteins, Anaphase-Promoting Complex-Cyclosome, Securin, Checkpoint Kinase 2
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