Checking in on Cds1 (Chk2): A checkpoint kinase and tumor suppressor

@article{McGowan2002CheckingIO,
  title={Checking in on Cds1 (Chk2): A checkpoint kinase and tumor suppressor},
  author={Clare H. McGowan},
  journal={BioEssays},
  year={2002},
  volume={24}
}
Together, DNA repair and checkpoint responses ensure the integrity of the genome. Coordination of cell cycle checkpoints and DNA repair are especially important following genotoxic radiation or chemotherapy, during which unusually high loads of DNA damage are sustained. In mammalian cells, the checkpoint kinase, Cds1 (also known as Chk2) is activated by ATM in response to DNA damage. The role of Cds1 as a checkpoint kinase depends on its ability to phosphorylate cell cycle regulators such p53… 
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References

SHOWING 1-10 OF 85 REFERENCES
Threonine 68 is required for radiation-induced phosphorylation and activation of Cds1
TLDR
Threonine 68 of Cds1 is the preferred site of phosphorylation by ATM in vitro, and is the principal irradiation-induced site ofosphorylation in vivo, which is demonstrated by the failure of a mutant, non-phosphorylatable form of CDS1 to be fully activated, and by its reduced ability to induce G1 arrest in response to ionising radiation.
Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway
TLDR
Results suggest that Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway and might not only delay mitotic entry, but also increase the capacity of cultured cells to survive after treatment with γ-radiation or with the topoisomerase-I inhibitor topotecan.
Linkage of ATM to cell cycle regulation by the Chk2 protein kinase.
TLDR
Chk2, the mammalian homolog of the Saccharomyces cerevisiae Rad53 and Schizosac charomyces pombe Cds1 protein kinases required for the DNA damage and replication checkpoints, was identified and phosphorylated and activated in response to replication blocks and DNA damage.
Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1 or Chk1
TLDR
It is concluded that both Cds1 and Chk1 regulate the binding of Cdc25 to 14-3-3 proteins as part of the checkpoint response to unreplicated DNA.
The ATM–Chk2–Cdc25A checkpoint pathway guards against radioresistant DNA synthesis
TLDR
A functional link between ATM, the checkpoint signalling kinase Chk2/Cds1 (Chk2) and Cdc25A is reported, and this mechanism in controlling the S-phase checkpoint is identified as a genomic integrity checkpoint that prevents radioresistant DNA synthesis.
Replication checkpoint enforced by kinases Cds1 and Chk1.
TLDR
Cds1 and Chk1 appear to jointly enforce the replication checkpoint, and HU-induced arrest of cell division was abolished in cds1 chk1 cells.
Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms.
TLDR
A model in which Chk1 and Rad53 function in parallel through Pds1 and Cdc5, respectively, to prevent anaphase entry and mitotic exit after DNA damage is supported, providing a possible explanation for the role of CDC5 in DNA damage checkpoint adaptation.
Mrc1 channels the DNA replication arrest signal to checkpoint kinase Cds1
TLDR
A novel checkpoint gene in fission yeast, mrc1 (mediator of replication checkpoint), is described that confers activation of the checkpoint kinase Cds1 to DNA synthesis (S) phase.
Rapid destruction of human Cdc25A in response to DNA damage.
TLDR
These results identify specific degradation of Cdc25A as part of the DNA damage checkpoint mechanism and suggest how CDC25A overexpression in human cancers might contribute to tumorigenesis.
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