Cited by 245DNA Repair MechanismsCancer-related Molecular PathwaysMicrotubule and mitosis dynamics

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Human Claspin Is Required for Replication Checkpoint Control

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Chini, Claudia Christiano Silva, Chen, Junjie·2003·Journal of Biological Chemistry

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Abstract

Claspin is a newly identified protein that regulates Chk1 activation in Xenopus. In the present study we investigated the role of human Claspin in the DNA damage/replication checkpoint in mammalian cells. We observed that human Claspin is a cell cycle regulated protein that peaks at S/G2 phase. Claspin localizes in the nuclei, but it only associates with Chk1 following replication stress or other types of DNA damage. In addition, Claspin is phosphorylated in response to replication stress, and this phosphorylation appears to be required for its association with Chk1. Moreover, Claspin interacts with the checkpoint proteins ATR and Rad9. Given that both the ATR and Rad9-Rad1-Hus1 complexes are involved in Chk1 activation, it is possible that Claspin works as an adaptor molecule bringing these molecules together. Using small interfering RNA technology, we have shown that down-regulation of Claspin expression inhibits Chk1 activation in response to replication stress. More importantly, down-regulation of Claspin augments the premature chromatin condensation induced by hydroxyurea, inhibits the UV-induced reduction of DNA synthesis, and decreases cell survival. Taken together, these data imply a potentially critical role for Claspin in replication checkpoint control in mammalian cells.

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Authors: Chini, C. C. S., & Chen, J.
Affiliations: Mayo Clinic (US)
Corresponding author: Chen, Junjie
ORCID: Chini, Claudia Christiano Silva
Chen, Junjie
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2003-08
Volume: 278
Issue: 32
Pages: 30057-30062
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m301136200
OpenAlex: W2137310763
Cited by: 244
References: 39
Citations by year: 2026: 3 · 2025: 6 · 2024: 2 · 2023: 9 · 2022: 2 · 2021: 9 · 2020: 8 · 2019: 13 · 2018: 5 · 2017: 8 · 2016: 12 · 2015: 11 · 2014: 8 · 2013: 10 · 2012: 15
FWCI: 5.64
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6269 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Mayo Clinic
National Institutes of Health
National Cancer Institute (R01CA089239, R01 CA 89239, R01CA092312, CA92312)
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, S-phase checkpoint, DNA damage checkpoint, Chk1 activation, ATR, protein phosphorylation, replication stress, cell cycle regulation, chromatin condensation, hydroxyurea, adaptor proteins
MeSH terms: Carrier Proteins, Cell Cycle, Cell Line, Cell Survival, Chromatin, DNA, DNA Damage, DNA-Binding Proteins, Endonucleases, HeLa Cells, Humans, Hydroxyurea, Microscopy, Fluorescence, Mitosis, Phosphorylation, Precipitin Tests, Time Factors, Transfection, Tumor Cells, Cultured, Ultraviolet Rays, Down-Regulation, G2 Phase, S Phase, Protein Serine-Threonine Kinases, Cell Cycle Proteins, K562 Cells, Schizosaccharomyces pombe Proteins, Xenopus Proteins, RNA, Small Interfering, Adaptor Proteins, Signal Transducing, Ataxia Telangiectasia Mutated Proteins

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Human Claspin Is Required for Replication Checkpoint Control

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