Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25.

@article{Snchez1997ConservationOT,
  title={Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25.},
  author={Yolanda S{\'a}nchez and C Wong and Richard Thoma and Ronald Richman and Z Wu and Helen Piwnica-Worms and Stephen J. Elledge},
  journal={Science},
  year={1997},
  volume={277 5331},
  pages={
          1497-501
        }
}
In response to DNA damage, mammalian cells prevent cell cycle progression through the control of critical cell cycle regulators. A human gene was identified that encodes the protein Chk1, a homolog of the Schizosaccharomyces pombe Chk1 protein kinase, which is required for the DNA damage checkpoint. Human Chk1 protein was modified in response to DNA damage. In vitro Chk1 bound to and phosphorylated the dual-specificity protein phosphatases Cdc25A, Cdc25B, and Cdc25C, which control cell cycle… 
Regulatory Interactions between the Checkpoint Kinase Chk1 and the Proteins of the DNA-dependent Protein Kinase Complex*
TLDR
A connection between components that regulate the checkpoint pathways and DNA-PK complex proteins, which have a role in the repair of double strand breaks are indicated.
Dual Regulation of Cdc25A by Chk1 and p53-ATF3 in DNA Replication Checkpoint Control*
TLDR
Two independent mechanisms acting in concert in regulation of Cdc25A in DNA damage response are revealed, and it is shown that inhibition of CDC25A transcription by p53-ATF3 is required for the maintenance of cell cycle arrest.
The Chk1 Protein Kinase and the Cdc25C Regulatory Pathways Are Targets of the Anticancer Agent UCN-01*
TLDR
Results identify the Chk1 kinase and the Cdc25C pathway as potential targets of G2 checkpoint abrogation by UCN-01, and cause loss of both serine 216 phosphorylation and 14-3-3 binding to CDC25C in DNA-damaged cells.
Two Distinct Cdc2 Pools Regulate Cell Cycle Progression and the DNA Damage Response in the Fission Yeast S.pombe
TLDR
S.pombe Cdc2 kinase exists in seven forms and the novel IEFPT technology, which combines isoelectric focusing with Phos-tag SDS electrophoresis (PT), adds support to the idea that two distinct CDC2 pools regulate cell cycle progression and the response to DNA damage.
SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase.
TLDR
A requirement for SCFbeta-TRCP in Cdc25A turnover during an unperturbed cell cycle and in response to DNA damage is demonstrated and roles for an additional kinase(s) in Chk1-dependent Cdc 25A turnover are suggested.
Differential Roles for Checkpoint Kinases in DNA Damage-dependent Degradation of the Cdc25A Protein Phosphatase*
TLDR
It is found that although Chk2 can phosphorylate many of the same sites in Cdc25A that Chk1 phosphorylates, albeit with reduced efficiency, Chk 2 is unable to efficientlyosphorylate Ser-76, which supports the idea that ChK1 is the primary signal transducer linking activation of the ATM/ATR kinases to CDC25A destruction in response to ionizing radiation.
CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage
TLDR
The results support a model in which, under normal cell cycle conditions and in the absence of DNA damage, CHK1 constitutively phosphorylatesCDC25B during interphase and thus prevents the premature initiation of mitosis by negatively regulating the activity of CDC25B at the centrosome.
Phosphorylation activates Chk1 and is required for checkpoint-mediated cell cycle arrest
TLDR
A kinase assay for Chk1 is developed, and it is shown that basal Chk2 kinase activity is increased in response to DNA damage and that this increase, but not the basal activity, is dependent on S345, and that S345 phosphorylation is required for an intact checkpoint response.
Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216.
TLDR
Results indicate that serine-216 phosphorylation and 14-3-3 binding negatively regulate Cdc25C and identify CDC25C as a potential target of checkpoint control in human cells.
Regulation of Chk1 Includes Chromatin Association and 14-3-3 Binding following Phosphorylation on Ser-345*
TLDR
The results indicate that there is more than one step in Chk1 activation and that the regulation of this checkpoint signaling is achieved at least in part through phosphorylation of Ser-345, which serves to localize Chk 1 in the nucleus presumably by blocking Crm1-dependent nuclear export.
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TLDR
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TLDR
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TLDR
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TLDR
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