| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.58703011 |
| Claspin is a large acidic protein that becomes phosphorylated and binds to Chk 1 in the presence of checkpoint inducing DNA templates in Xenopus egg extracts . 0.58703011^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.79973987 |
| In addition , Claspin is phosphorylated in response to replication stress , and this phosphorylation appears to be required for its association with Chk 1 . 0.79973987^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.87352967 |
| Claspin associates with Chk 1 upon replication stress and DNA damage and is required for Chk 1 activation in both Xenopus and human systems . 0.87352967^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Claspin , a novel protein required for the activation of Chk 1 during a DNA replication checkpoint response in Xenopus egg extracts . ^^^ We have identified Claspin , a novel protein that binds to Xenopus Chk 1 ( Xchk 1 ) . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Claspin , a Chk 1 regulatory protein , monitors DNA replication on chromatin independently of RPA , ATR , and Rad 17 . ^^^ Claspin is required for the ATR dependent activation of Chk 1 in Xenopus egg extracts containing incompletely replicated DNA . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Phosphorylated claspin interacts with a phosphate binding site in the kinase domain of Chk 1 during ATR mediated activation . ^^^ Claspin is essential for the ATR dependent activation of Chk 1 in Xenopus egg extracts containing incompletely replicated or UV damaged DNA . ^^^ The activated form of Claspin contains two repeated phosphopeptide motifs that mediate its binding to Chk 1 . ^^^ Mutagenesis of these residues strongly compromises the ability of Chk 1 to interact with Claspin . ^^^ The predicted position on Chk 1 of the phosphate group from Claspin corresponds to the location of activation loop phosphorylation in various kinases . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| DNA damage induces the formation of a complex between Claspin and BRCA 1 , a second regulator of Chk 1 activation . ^^^ BRCA 1 and Claspin then function to activate the tumor suppressor Chk 1 . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| The checkpoint mediator protein Claspin is essential for the ATR dependent activation of Chk 1 in Xenopus egg extracts containing aphidicolin induced DNA replication blocks . ^^^ In this process , Claspin dissociates from chromatin , and Chk 1 undergoes inactivation . ^^^ Under such adaptation defective conditions , Claspin accumulates on chromatin at high levels , and Chk 1 does not decrease in activity . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| ATR , Claspin and the Rad 9 Rad1 Hus 1 complex regulate Chk 1 and Cdc25A in the absence of DNA damage . ^^^ ATR , with Claspin and the Rad 9 Rad1 Hus 1 complex , activates Chk 1 after DNA damage . ^^^ Here , we show that during physiological S phase the regulation of the Chk 1 Cdc25A pathway depends on ATR , Claspin , Rad 9 , and Hus 1 . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Claspin and the activated form of ATR ATRIP collaborate in the activation of Chk 1 . ^^^ Claspin is necessary for the ATR dependent activation of Chk 1 in Xenopus egg extracts containing incompletely replicated DNA . ^^^ We have studied the respective roles of ATR ATRIP and Claspin in the activation of Chk 1 . ^^^ Without Claspin , activated ATR ATRIP phosphorylated Chk 1 weakly in a cell free reaction . ^^^ The addition of Claspin to this reaction strongly stimulated the phosphorylation of Chk 1 by ATR ATRIP . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| DNA dependent phosphorylation of Chk 1 and Claspin in a human cell free system . ^^^ Phosphorylation of Chk 1 is dependent on the interaction of Claspin , a protein first identified in Xenopus as a Chk 1 binding protein . ^^^ We show that the DNA dependent binding of Chk 1 to Claspin requires two phosphorylation sites , Thr 916 and Ser 945 , which lie within the Chk 1 binding domain of Claspin . ^^^ Using a phosphopeptide derived from the consensus motif of these sites , we show that the interaction of Claspin with Chk 1 is required for the ATR / ATM dependent phosphorylation of Chk 1 . ^^^ Claspin is phosphorylated in the Chk 1 binding domain in an ATR / ATM dependent manner and is also targeted by additional kinases in response to double stranded DNA oligonucleotides . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Consistent with these events being triggered by active checkpoint signaling , inhibition of the DNA damage activated kinases ATR and ATM , or siRNA mediated downregulation of the DNA damage mediator proteins Claspin and TopBP 1 , impaired DNA damage induced dissociation of Chk 1 from chromatin . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Interestingly , phosphorylation of Rad 1 is independent of Claspin and the Rad 9 carboxy terminus , both of which are required for Chk 1 phosphorylation . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Chk 1 is required to maintain claspin stability . ^^^ Claspin is a Chk 1 interacting protein that participates in the DNA replication checkpoint . ^^^ In this study , we show that Claspin expression is downregulated by the proteasome mediated degradation pathway and that Chk 1 is required to maintain Claspin stability . ^^^ Downregulation of Chk 1 expression by siRNA or inhibition of Chk 1 activity by UCN 01 decreases Claspin levels in cells . ^^^ Conversely , overexpression of Chk 1 increases Claspin levels . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| The checkpoint mediator protein Claspin is indispensable for the ATR dependent phosphorylation of Chk 1 in response to stalled DNA replication forks in Xenopus egg extracts . ^^^ Significantly , removal of Claspin from egg extracts only partially abrogates the activation of Chk 1 in response to chromatin with DSBs , whereas depletion of both Claspin and BRCA 1 completely abolishes this activation . ^^^ Conversely , neither phosphorylation of Claspin on these sites nor the presence of BRCA 1 is necessary for activation of Chk 1 in response to stalled replication forks . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Cleavage of claspin by caspase 7 during apoptosis inhibits the Chk 1 pathway . ^^^ Claspin is required for the phosphorylation and activation of the Chk 1 protein kinase by ATR during DNA replication and in response to DNA damage . ^^^ Subsequently , etoposide caused activation of caspase 7 , cleavage of Claspin , and dephosphorylation of Chk 1 . ^^^ These results indicate that cleavage of Claspin by caspase 7 inactivates the Chk 1 signaling pathway . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Roles of replication fork interacting and Chk 1 activating domains from Claspin in a DNA replication checkpoint response . ^^^ Claspin is essential for the ATR dependent activation of Chk 1 in Xenopus egg extracts containing incompletely replicated DNA . ^^^ Absence of BP 1 has no effect on the ability of Claspin to mediate activation of Chk 1 . ^^^ By contrast , removal of BP 2 causes a large reduction in the Chk 1 activating potency of Claspin . ^^^ We also find that Claspin contains a small Chk 1 activating domain ( residues 776 905 ) that does not bind stably to chromatin , but it is fully effective at high concentrations for mediating activation of Chk 1 . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Direct requirement for Xmus 101 in ATR mediated phosphorylation of Claspin bound Chk 1 during checkpoint signaling . ^^^ We find that Xmus 101 is essential for AT 70 mediated checkpoint signaling and that it functions to promote phosphorylation of Claspin bound Chk 1 by the ataxia telangiectasia and Rad 3 related ( ATR ) protein kinase . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Claspin is involved in ATR dependent activation of Chk 1 during DNA replication and in response to DNA damage . ^^^ Claspin is stabilized in S phase but is abruptly degraded in mitosis and is absent from early G ( 1 ) cells in which the phosphorylation of Chk 1 by ATR is abrogated . ^^^ In response to hydroxyurea , UV or aphidicolin , Claspin is phosphorylated in the Chk 1 binding domain and its protein levels are increased in an ATR dependent manner . ^^^ Thus , the Chk 1 pathway is regulated through both phosphorylation of Claspin and its controlled degradation . . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Claspin operates downstream of TopBP 1 to direct ATR signaling towards Chk 1 activation . ^^^ TopBP 1 and Claspin are adaptor proteins that facilitate phosphorylation of Chk 1 by the ATR kinase in response to genotoxic stress . ^^^ Despite their established requirement for Chk 1 activation , the exact way in which TopBP 1 and Claspin control Chk 1 phosphorylation remains unclear . ^^^ In contrast , Claspin , like Chk 1 , remained distributed throughout the nucleus both before and after DNA damage . ^^^ Consistently , the RNAi mediated ablation of Claspin selectively abrogated ATR ' s ability to phosphorylate Chk 1 but not other ATR targets . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Destruction of Claspin by SCFbetaTrCP restrains Chk 1 activation and facilitates recovery from genotoxic stress . ^^^ We show that Claspin , an adaptor protein required for Chk 1 activation , becomes degraded at the onset of mitosis . ^^^ Uncoupling of Claspin from betaTrCP by mutating the conserved serines in Claspin ' s phosphodegron or by knocking down betaTrCP stabilized Claspin in mitosis , impaired Chk 1 dephosphorylation , and delayed G2 / M transition during recovery from cell cycle arrest imposed by DNA damage or replication stress . ^^^ Moreover , the inability to degrade Claspin allowed partial reactivation of Chk 1 in cells exposed to DNA damage after passing the G2 / M transition . ^^^ Our data suggest that degradation of Claspin facilitates timely reversal of the checkpoint response and delineates the period permissive for Chk 1 activation during cell cycle progression . . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| During replicative stress , Claspin mediates the phosphorylation and consequent activation of Chk 1 by ATR . ^^^ Significantly , expression of a stable Claspin mutant unable to bind betaTrCP prolongs the activation of Chk 1 , thereby attenuating the recovery from the DNA replication stress response and significantly delaying entry into mitosis . ^^^ |
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| Interacting proteins: Q9HAW4 and O14757 |
Pubmed |
SVM Score :0.0 |
| Rad 17 phosphorylation is required for claspin recruitment and Chk 1 activation in response to replication stress . ^^^ These findings reveal a phosphorylation dependent function of Rad 17 in an ATR Rad 17 Claspin Chk 1 signaling cascade that responds to specific replication stress . . ^^^ |
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