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Role for casein kinase 1 in the phosphorylation of Claspin on critical residues necessary for the activation of Chk1

Meng, Zheng and Capalbo, Luisa and Glover, David M. and Dunphy, William G. (2011) Role for casein kinase 1 in the phosphorylation of Claspin on critical residues necessary for the activation of Chk1. Molecular Biology of the Cell, 22 (16). pp. 2834-2847. ISSN 1059-1524. PMCID PMC3154880.

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The mediator protein Claspin is critical for the activation of the checkpoint kinase Chk1 during checkpoint responses to stalled replication forks. This function involves the Chk1-activating domain (CKAD) of Claspin, which undergoes phosphorylation on multiple conserved sites. These phosphorylations promote binding of Chk1 to Claspin and ensuing activation of Chk1 by ATR. However, despite the importance of this regulatory process, the kinase responsible for these phosphorylations has remained unknown. By using a multifaceted approach, we have found that casein kinase 1 gamma 1 (CK1γ1) carries out this function. CK1γ1 phosphorylates the CKAD of Claspin efficiently in vitro, and depletion of CK1γ1 from human cells by small interfering RNA (siRNA) results in dramatically diminished phosphorylation of Claspin. Consequently, the siRNA-treated cells display impaired activation of Chk1 and resultant checkpoint defects. These results indicate that CK1γ1 is a novel component of checkpoint responses that controls the interaction of a key checkpoint effector kinase with its cognate mediator protein.

Item Type:Article
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URLURL TypeDescription DOIArticle CentralArticle
Glover, David M.0000-0003-0956-0103
Dunphy, William G.0000-0001-7598-8939
Additional Information:© 2011 The American Society of Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license ( Submitted January 18, 2011. Revised May 3, 2011. Accepted June 7, 2011. This article was published online ahead of print in MBoC in Press ( on June 16, 2011. We are grateful to laboratory members for helpful advice and comments on the manuscript. We also thank Rochelle Diamond for assistance with flow cytometry and J. Jiang (University of Texas Southwestern Medical School, Dallas, TX) for Drosophila casein kinase expression vectors. This work was supported by National Institutes of Health grants GM-043974 and GM-070891 and an Ellison Senior Scholar in Aging award to W.G.D. Work in the laboratory of D.M.G. was supported by Cancer Research UK and the Biotechnology and Biological Sciences Research Council (United Kingdom).
Funding AgencyGrant Number
Ellison Senior Scholar in AgingUNSPECIFIED
Biotechnology and Biological Sciences Research Council (BBSRC)UNSPECIFIED
Issue or Number:16
PubMed Central ID:PMC3154880
Record Number:CaltechAUTHORS:20110829-104551403
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:25143
Deposited By: Tony Diaz
Deposited On:07 Sep 2011 15:53
Last Modified:09 Mar 2020 13:18

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