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PMID:16963448

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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

Significance

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


See also

References

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