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The conserved C terminus of Claspin interacts with Rad9 and promotes rapid activation of Chk1.
Liu S
,
Song N
,
Zou L
.
???displayArticle.abstract??? Claspin is a key mediator of the ATR-Chk1 checkpoint pathway. In response to DNA damage, Claspin interacts with Rad17 and Chk1 in a phosphorylation-dependent manner, enabling ATR to phosphorylate Chk1 efficiently. Claspin also interacts with Rad9, but how they interact and whether the interaction is functional remains unknown. Unexpectedly, our analysis of two splicing isoforms of Claspin provided an answer to these questions. The Claspin(1339) isoform contains an evolutionarily conserved C terminus, but the Claspin(1332) isoform does not. Although the transcripts encoding both Claspin isoforms coexist in HCT116 cells, Claspin(1339) is the predominant form responsible for Chk1 activation. When expressed in cells depleted of endogenous Claspin, both Claspin(1339) and Claspin(1332) are able to mediate Chk1 activation. However, the activation of Chk1 is delayed in Claspin(1332)-expressing cells compared with Claspin(1339)-expressing cells. Furthermore, only Claspin(1339) but not Claspin(1332) interacts with Rad9 efficiently. Together, these results suggest that the conserved C terminus of Claspin interacts with Rad9 and ensures timely activation of the ATR-Chk1 pathway.
Bennett,
Regulation of Claspin degradation by the ubiquitin-proteosome pathway during the cell cycle and in response to ATR-dependent checkpoint activation.
2006, Pubmed
Bennett,
Regulation of Claspin degradation by the ubiquitin-proteosome pathway during the cell cycle and in response to ATR-dependent checkpoint activation.
2006,
Pubmed
Bensimon,
Beyond ATM: the protein kinase landscape of the DNA damage response.
2011,
Pubmed
Chini,
Chk1 is required to maintain claspin stability.
2006,
Pubmed
Chini,
Human claspin is required for replication checkpoint control.
2003,
Pubmed
,
Xenbase
Ciccia,
The DNA damage response: making it safe to play with knives.
2010,
Pubmed
Clarke,
DNA-dependent phosphorylation of Chk1 and Claspin in a human cell-free system.
2005,
Pubmed
,
Xenbase
Ellison,
Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5' recessed DNA.
2003,
Pubmed
Flynn,
ATR: a master conductor of cellular responses to DNA replication stress.
2011,
Pubmed
Focarelli,
Claspin inhibition leads to fragile site expression.
2009,
Pubmed
Jackson,
The DNA-damage response in human biology and disease.
2009,
Pubmed
Jeong,
Phosphorylated claspin interacts with a phosphate-binding site in the kinase domain of Chk1 during ATR-mediated activation.
2003,
Pubmed
,
Xenbase
Kumagai,
Claspin and the activated form of ATR-ATRIP collaborate in the activation of Chk1.
2004,
Pubmed
,
Xenbase
Kumagai,
TopBP1 activates the ATR-ATRIP complex.
2006,
Pubmed
,
Xenbase
Kumagai,
Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Kumagai,
Repeated phosphopeptide motifs in Claspin mediate the regulated binding of Chk1.
2003,
Pubmed
,
Xenbase
Lee,
Rad17 plays a central role in establishment of the interaction between TopBP1 and the Rad9-Hus1-Rad1 complex at stalled replication forks.
2010,
Pubmed
,
Xenbase
Lee,
Claspin, a Chk1-regulatory protein, monitors DNA replication on chromatin independently of RPA, ATR, and Rad17.
2003,
Pubmed
,
Xenbase
Lindsey-Boltz,
Reconstitution of human claspin-mediated phosphorylation of Chk1 by the ATR (ataxia telangiectasia-mutated and rad3-related) checkpoint kinase.
2009,
Pubmed
,
Xenbase
Liu,
Claspin operates downstream of TopBP1 to direct ATR signaling towards Chk1 activation.
2006,
Pubmed
Lupardus,
A requirement for replication in activation of the ATR-dependent DNA damage checkpoint.
2002,
Pubmed
,
Xenbase
Mailand,
Destruction of Claspin by SCFbetaTrCP restrains Chk1 activation and facilitates recovery from genotoxic stress.
2006,
Pubmed
Meng,
Role for casein kinase 1 in the phosphorylation of Claspin on critical residues necessary for the activation of Chk1.
2011,
Pubmed
Namiki,
ATRIP associates with replication protein A-coated ssDNA through multiple interactions.
2006,
Pubmed
Peschiaroli,
SCFbetaTrCP-mediated degradation of Claspin regulates recovery from the DNA replication checkpoint response.
2006,
Pubmed
Petermann,
Claspin promotes normal replication fork rates in human cells.
2008,
Pubmed
Serçin,
Characterization of functional domains in human Claspin.
2011,
Pubmed
Wang,
Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress.
2006,
Pubmed
Yang,
Chk1 and Claspin potentiate PCNA ubiquitination.
2008,
Pubmed
Zhang,
Prevalence and functional analysis of sequence variants in the ATR checkpoint mediator Claspin.
2009,
Pubmed
Zou,
Replication protein A-mediated recruitment and activation of Rad17 complexes.
2003,
Pubmed
Zou,
Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin.
2002,
Pubmed
Zou,
Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.
2003,
Pubmed
