PMID:16963448

Citation	Chini, CC and Chen, J (2006) Repeated phosphopeptide motifs in human Claspin are phosphorylated by Chk1 and mediate Claspin function. J. Biol. Chem. 281:33276-82
Abstract	Claspin is a checkpoint protein involved in ATR (ataxia telangiectasia mutated- and Rad3-related)-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 becomes 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 Thr-916 in response to replication stress and UV damage. Mutation of these phosphorylation sites on Claspin inhibited Claspin-Chk1 interaction in vivo, impaired Chk1 activation, and induced premature chromatin condensation in cells, indicating a defect in replication checkpoint. In addition, we found that Thr-916 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.
Links	PubMed Online version:10.1074/jbc.M604373200
Keywords	Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Cell Line; Humans; Phosphopeptides/metabolism; Phosphorylation; Phosphothreonine/metabolism; Protein Binding; Protein Kinases/genetics; Protein Kinases/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:CHK1	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q9HAW4	F		Seeded From UniProt	complete
HUMAN:CLSPN	involved_in	GO:0000077: DNA damage checkpoint	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CLSPN	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:O14757	F		Seeded From UniProt	complete
HUMAN:CHK1	involved_in	GO:0000077: DNA damage checkpoint	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CHK1	enables	GO:0004674: protein serine/threonine kinase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:CHK1	involved_in	GO:0006975: DNA damage induced protein phosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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