hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response

@article{Lee2000hCds1mediatedPO,
  title={hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response},
  author={Jong-Soo Lee and Kimberly M. Collins and Alexandra L. Brown and Chang-Hun Lee and Jay H. Chung},
  journal={Nature},
  year={2000},
  volume={404},
  pages={201-204}
}
Mutations in the BRCA1 (ref. 1) tumour suppressor gene are found in almost all of the families with inherited breast and ovarian cancers and about half of the families with only breast cancer. Although the biochemical function of BRCA1 is not well understood, it is important for DNA damage repair and cell-cycle checkpoint. BRCA1 exists in nuclear foci but is hyperphosphorylated and disperses after DNA damage. It is not known whether BRCA1 phosphorylation and dispersion and its function in DNA… 
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  • Biology, Medicine
    Biochemical and biophysical research communications
  • 2007
The phosphorylation state of the tumor suppressor protein BRCA1 is tightly associated with its functions including cell cycle control and DNA repair. Protein kinases involved in the DNA damage…
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Findings suggest that the ring domain mediates critical protein interactions, and disruption of which contributes to carcinogenesis, and hint at diverse roles of BRCA1 in multiple cellular processes.
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TLDR
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BRCA1 through its association with specific proteins and multi-protein complexes is a sentinel of the normal cell cycle control and DNA repair, and is implicated in DNA repair mechanisms and cell cycle checkpoint control.
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References

SHOWING 1-10 OF 30 REFERENCES
Dynamic Changes of BRCA1 Subnuclear Location and Phosphorylation State Are Initiated by DNA Damage
TLDR
The data imply that the BRCA1 S phase foci are dynamic physiological elements, responsive to DNA damage, and that B RCA1-containing multiprotein complexes participate in a replication checkpoint response.
Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks.
TLDR
Results from this study indicate that the checkpoint protein kinase ATM (mutated in ataxia telangiectasia) was required for phosphorylation of Brca1 in response to ionizing radiation, which may provide a molecular explanation for the role of ATM in breast cancer.
BRCA1 Expression Restores Radiation Resistance in BRCA1-defective Cancer Cells through Enhancement of Transcription-coupled DNA Repair*
TLDR
It is shown that human cancer cells containing mutated BRCA1 are hypersensitive to ionizing radiation and this hypersensitivity can be reversed by the expression of forms of BRC a1 that are not growth suppressing.
Arrest of the cell cycle by the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAF1/CiPl
TLDR
It is shown that BRCA1 transactivates expression of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 in a p53-independent manner, and that B RCA1 inhibits cell-cycle progression into the S-phase following its transfection into human cancer cells.
Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response.
TLDR
It is shown that BRCA1 interacts in vitro and in vivo with hRad50, which forms a complex with hMre11 and p95/nibrin that is important for the cellular responses to DNA damage that are mediated by the h Rad50-hMre 11-p95 complex.
BRCA1 required for transcription-coupled repair of oxidative DNA damage.
TLDR
It is shown that mouse embryonic stem cells deficient in BRCA1 are defective in the ability to carry out transcription-coupled repair of oxidative DNA damage, and are hypersensitive to ionizing radiation and hydrogen peroxide.
Induction of phosphorylation on BRCA1 during the cell cycle and after DNA damage.
TLDR
The results indicate that BRCA1 undergoes cyclic hyperphosphorylation during the cell cycle; however, this modification, as well as changes in B RCA1 nuclear staining, also occurs in response to DNA damage.
A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase
TLDR
The results suggest that, in human cells, the DNA-damage checkpoint involves direct inactivation of Cdc25 catalyzed by Cds1 and/or Chk1, which is homologous to the CDS1/Rad53 family of checkpoint kinases in yeast.
A targeted disruption of the murine Brca1 gene causes γ-irradiation hypersensitivity and genetic instability
TLDR
It is directly demonstrated that BRCA1 is responsible for the integrity of the genome and the increased incidence of such additional mutations accounts for the mechanism of tumorigenesis associated with Brca1 mutations in humans.
Brca1 controls homology-directed DNA repair.
TLDR
A caretaker role for BRCA1 is demonstrated in preserving genomic integrity by promoting homologous recombination and limiting mutagenic nonhomologous repair processes.
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