Cited by 430DNA Repair MechanismsCancer-related Molecular PathwaysMicrotubule and mitosis dynamics

Claspin, a Novel Protein Required for the Activation of Chk1 during a DNA Replication Checkpoint Response in Xenopus Egg Extracts

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Kumagai, Akiko, Dunphy, William G.·2000·Molecular Cell

Abstract

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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Crossref · 10.1016/s1097-2765(05)00092-4

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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
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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