Cited by 536DNA Repair MechanismsMicrotubule and mitosis dynamicsFungal and yeast genetics research

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Control of the DNA Damage Checkpoint by Chk1 and Rad53 Protein Kinases Through Distinct Mechanisms

Sanchez, Yolanda, Bachant, Jeff, Wang, Hong, Hu, Fenghua, Liu, Dou, Tetzlaff, Michael, Elledge, Stephen J.·1999·Science

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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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Jackson, S. P. (2005) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1028354.343449
Faculty Opinions recommendation of Direct kinase-to-kinase signaling mediated by the FHA phosphoprotein recognition domain of the Dun1 DNA damage checkpoint kinase.
Jackson, S. P. (2003) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1000241.185118
Protein kinase (CaMK, MLCK, PhK, SNF, KIN, NIM1, MAPKAP, POLO, CHK, ULK, RSK-2nd domain)
(2007) · Springer eBooks · doi:10.1007/978-3-540-49756-1_62
Cell Cycle Checkpoints
Friedberg, E. C., Walker, G. C., Siede, W., Wood, R. D., Schultz, R. A., & Ellenberger, T. E. (2014) · ASM Press eBooks · doi:10.1128/9781555816704.ch21

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.
ORCID: Bachant, Jeff
Hu, Fenghua
Elledge, Stephen J.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1999-11-05
Volume: 286
Issue: 5442
Pages: 1166-1171
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.286.5442.1166
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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Control of the DNA Damage Checkpoint by Chk1 and Rad53 Protein Kinases Through Distinct Mechanisms

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