Claspin, a Novel Protein Required for the Activation of Chk1 during a DNA Replication Checkpoint Response in Xenopus Egg Extracts
Open accessAbstract
We have identified Claspin, a novel protein that binds to Xenopus Chk1 (Xchk1). Binding of Claspin to Xchk1 is highly elevated in the presence of DNA templates that trigger a checkpoint arrest of the cell cycle in Xenopus egg extracts. Xchk1 becomes phosphorylated during a checkpoint response, and we demonstrate directly that this phosphorylation results in the activation of Xchk1. Immunodepletion of Claspin from egg extracts abolishes both the phosphorylation and activation of Xchk1. Furthermore, Claspin-depleted extracts are unable to arrest the cell cycle in response to DNA replication blocks. Taken together, these findings indicate that Claspin is an essential upstream regulator of Xchk1.
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Claspin is required for ATR-Chk1 checkpoint activation.
“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 [127]
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- Authors
- Kumagai, A., & Dunphy, W. G.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Dunphy, William G.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 6
- Issue
- 4
- Pages
- 839-849
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1999554125
- Cited by
- 430
- References
- 36
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 15 · 2023: 11 · 2022: 9 · 2021: 13 · 2020: 11 · 2019: 12 · 2018: 20 · 2017: 12 · 2016: 16 · 2015: 14 · 2014: 22 · 2013: 19 · 2012: 16
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- 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
- Claspin, Chk1, DNA replication checkpoint, checkpoint activation, protein phosphorylation, cell cycle arrest, replication stress, Xenopus egg extracts
- MeSH terms
- Checkpoint Kinase 1, Amino Acid Sequence, Animals, Carrier Proteins, Cell Cycle, Cell-Free System, Cloning, Molecular, DNA Replication, Enzyme Activation, Female, Humans, Molecular Sequence Data, Oocytes, Phosphorylation, Protein Kinases, Recombinant Proteins, Templates, Genetic, Xenopus laevis, Sequence Alignment, Sequence Homology, Amino Acid, Xenopus Proteins, Adaptor Proteins, Signal Transducing
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