The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Conservation of the Chk1 Checkpoint Pathway in Mammals: Linkage of DNA Damage to Cdk Regulation Through Cdc25
Abstract
In response to DNA damage, mammalian cells prevent cell cycle progression through the control of critical cell cycle regulators. A human gene was identified that encodes the protein Chk1, a homolog of the Schizosaccharomyces pombe Chk1 protein kinase, which is required for the DNA damage checkpoint. Human Chk1 protein was modified in response to DNA damage. In vitro Chk1 bound to and phosphorylated the dual-specificity protein phosphatases Cdc25A, Cdc25B, and Cdc25C, which control cell cycle transitions by dephosphorylating cyclin-dependent kinases. Chk1 phosphorylates Cdc25C on serine-216. As shown in an accompanying paper by Peng et al . in this issue, serine-216 phosphorylation creates a binding site for 14-3-3 protein and inhibits function of the phosphatase. These results suggest a model whereby in response to DNA damage, Chk1 phosphorylates and inhibits Cdc25C, thus preventing activation of the Cdc2–cyclin B complex and mitotic entry.
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“The phosphorylation of Chk1 enhances Chk1’s kinase activity, which in turn phosphorylates downstream substrates (e.g., Cdc25, BLM, and FANCD2/FANCE) and facilitates cell cycle arrest and DNA damage repair [91–93].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [91]
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Cites
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Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
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Self-citationCell Cycle Checkpoints: Preventing an Identity Crisis
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Self-citationRadiation-induced cell cycle arrest compromised by p21 deficiency
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Fission yeast chkl protein kinase links the rad checkpoint pathway to cdc2
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Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibiting cdc2 by Y15 phosphorylation
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rad -Dependent Response of the chk1 -Encoded Protein Kinase at the DNA Damage Checkpoint
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Research works printed but not linked: 3
- Waldman T., et al., ibid. 381, 713 (1996).
- Vorechovsky I., et al., Cancer Res. 56, 2726 (1996);
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Cellular processing of platinum anticancer drugs
Wang, D., & Lippard, S. J. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1691 · Cited by 3,801
Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints
Sancar, A., Lindsey-Boltz, L. A., Ünsal-Kaçmaz, K., & Linn, S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073723 · Cited by 3,317
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-citationDNA double-strand breaks: signaling, repair and the cancer connection
Khanna, K. K., & Jackson, S. P. (2001) · Nature Genetics · doi:10.1038/85798 · Cited by 2,455
Cell cycle checkpoint signaling through the ATM and ATR kinases
Abraham, R. T. (2001) · Genes & Development · doi:10.1101/gad.914401 · Cited by 1,966
Metadata
- Authors
- Sanchez, Y., Wong, C., Thoma, R. S., Richman, R., Wu, Z., Piwnica-Worms, H., & Elledge, S. J.
- Affiliations
- Y. Sanchez, C. Wong, S. J. Elledge, Verna and Marrs McLean Department of Biochemistry, Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
- Howard Hughes Medical Institute (US)
- Venue
- Science
- Published
- 1997-09-05
- Volume
- 277
- Issue
- 5331
- Pages
- 1497-1501
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2105592350
- Cited by
- 1,320
- References
- 24
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 14 · 2023: 32 · 2022: 29 · 2021: 25 · 2020: 30 · 2019: 22 · 2018: 22 · 2017: 35 · 2016: 34 · 2015: 39 · 2014: 29 · 2013: 37 · 2012: 39
- FWCI
- 30.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1f32gm017763-01)
- National Institute of General Medical Sciences (GM-44664, GM17763)
- 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 › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- Chk1, DNA damage checkpoint, Cdc25 phosphatase, cyclin-dependent kinases, cell cycle regulation, 14-3-3 protein binding, mitotic entry, protein kinases, mammalian cells
- MeSH terms
- Checkpoint Kinase 1, F-Box-WD Repeat-Containing Protein 7, Amino Acid Sequence, Animals, Chromosome Mapping, Chromosomes, Human, Pair 11, Cytoskeletal Proteins, DNA Damage, HeLa Cells, Humans, Mitosis, Molecular Sequence Data, Phosphoprotein Phosphatases, Phosphorylation, Phosphoserine, Protein Kinases, Proteins, Recombinant Fusion Proteins, Transfection, Tyrosine 3-Monooxygenase, Signal Transduction, G2 Phase, CDC2 Protein Kinase, Protein Tyrosine Phosphatases, Cell Cycle Proteins, cdc25 Phosphatases, Schizosaccharomyces pombe Proteins, Ubiquitin-Protein Ligases, F-Box Proteins, 14-3-3 Proteins, Mice
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