Replication Checkpoint Enforced by Kinases Cds1 and Chk1
Abstract
Cdc2, the kinase that induces mitosis, is regulated by checkpoints that couple mitosis to the completion of DNA replication and repair. The repair checkpoint kinase Chk1 regulates Cdc25, a phosphatase that activates Cdc2. Effectors of the replication checkpoint evoked by hydroxyurea (HU) are unknown. Treatment of fission yeast with HU stimulated the kinase Cds1, which appears to phosphorylate the kinase Wee1, an inhibitor of Cdc2. The protein kinase Cds1 was also required for a large HU-induced increase in the amount of Mik1, a second inhibitor of Cdc2. HU-induced arrest of cell division was abolished in cds1 chk1 cells. Thus, Cds1 and Chk1 appear to jointly enforce the replication checkpoint.
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Chk1 phosphorylation increases its kinase activity, allowing it to phosphorylate substrates such as Cdc25, BLM, and FANCD2/FANCE and to promote cell cycle arrest and DNA repair.
“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 [92]
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- Authors
- Boddy, M. N., Furnari, B., Mondesert, O., & Russell, P.
- Affiliations
- Scripps Research Institute (US)
- Departments of Molecular Biology and Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
- Corresponding author
- Russell, Paul
- Venue
- Science
- Published
- 1998-05-08
- Volume
- 280
- Issue
- 5365
- Pages
- 909-912
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2049508647
- Cited by
- 316
- References
- 13
- Citations by year
- 2026: 3 · 2025: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 7 · 2014: 8 · 2013: 4 · 2012: 12
- FWCI
- 12.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- 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
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- S-phase checkpoint, Chk1, cdc2 kinase, WEE1, Cdc25 phosphatase, hydroxyurea, cell cycle arrest, DNA replication, Schizosaccharomyces pombe, mitosis
- MeSH terms
- Checkpoint Kinase 1, Cell Cycle, DNA Repair, DNA Replication, Hydroxyurea, Nuclear Proteins, Phosphoprotein Phosphatases, Phosphorylation, Protein Kinases, Protein-Tyrosine Kinases, Recombinant Fusion Proteins, Schizosaccharomyces, S Phase, CDC2 Protein Kinase, Protein Serine-Threonine Kinases, Cell Cycle Proteins, cdc25 Phosphatases, Schizosaccharomyces pombe Proteins, Checkpoint Kinase 2
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