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Papers In Press, published online ahead of print September 8, 2006
Department of Oncology Research, Mayo Clinic, Rochester, MN 55905
Corresponding Author: chen.junjie{at}mayo.edu
Claspin is a checkpoint protein involved in ATR-dependent Chk1 activation in Xenopus and human cells. In Xenopus, Claspin interacts with Chk1 after DNA damage through a region containing two highly conserved repeats which became phosphorylated during the checkpoint response. Because this region is also conserved in human Claspin, we investigated the regulation and function of these potential phosphorylation sites in human Claspin. We found that Claspin is phosphorylated in vivo at Thr916 in response to replication stress and UV damage. Mutation of these phosphorylation sites on Claspin inhibits Claspin-Chk1 interaction in vivo, impairs Chk1 activation and induces Premature Chromatin Condensation (PCC) in cells, indicating a defect in replication checkpoint. In addition, we found that Thr916 on Claspin is phosphorylated by Chk1, suggesting that Chk1 regulates Claspin during checkpoint response. These results together indicate that phosphorylation of Claspin repeats in human Claspin is important for Claspin function and the regulation of Claspin-Chk1 interaction in human cells.
J. Biol. Chem, 10.1074/jbc.M604373200
Submitted on May 8, 2006
Revised on September 7, 2006
Accepted on September 8, 2006
Repeated phosphopeptide motifs in human claspin are phosphorylated by CHK1 and mediate claspin function
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