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Repeated phosphopeptide motifs in Claspin mediate the regulated binding of Chk1

Kumagai, Akiko and Dunphy, William G. (2003) Repeated phosphopeptide motifs in Claspin mediate the regulated binding of Chk1. Nature Cell Biology, 5 (2). pp. 161-165. ISSN 1465-7392.

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In vertebrates, the checkpoint-regulatory kinase Chk1 mediates cell-cycle arrest in response to a block in DNA replication or to DNA damaged by ultraviolet radiation. The activation of Chk1 depends on both Claspin and the upstream regulatory kinase ATR. Claspin is a large acidic protein that becomes phosphorylated and binds to Chk1 in the presence of checkpoint-inducing DNA templates in Xenopus egg extracts. Here we identify, by means of deletion analysis, a region of Claspin of 57 amino acids that is both necessary and sufficient for binding to Xenopus Chk1. This Chk1-binding domain contains two highly conserved repeats of approximately ten amino acids. A serine residue in each repeat (serine 864 and serine 895) undergoes phosphorylation during a checkpoint response. A mutant of Claspin containing non-phosphorylatable amino acids at positions 864 and 895 cannot bind to Chk1 and is unable to mediate its activation. Our results indicate that two phosphopeptide motifs in Claspin are essential for checkpoint signalling.

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Kumagai, Akiko0000-0003-2422-8053
Dunphy, William G.0000-0001-7598-8939
Additional Information:© 2003 Nature Publishing Group. Received 4 July 2002; revised 15 October 2002; accepted 21 November 2002; published 20 January 2003. We thank T. Pogodin for technical assistance, S. Horvath for phosphopeptide synthesis, and members of the laboratory for comments on the manuscript. This work was supported in part by a grant from the NIH. W.G.D. is an investigator of the Howard Hughes Medical Institute.
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Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:2
Record Number:CaltechAUTHORS:20150401-131436483
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56293
Deposited By: Tony Diaz
Deposited On:01 Apr 2015 20:33
Last Modified:09 Mar 2020 13:18

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