Effect of DNA damage on a BRCA1 complex (original) (raw)

Tumour suppressors (Communication arising)

Nature volume 414, page 36 (2001)Cite this article

Abstract

The tumour-suppressor protein BRCA1 mediates its biological functions by interacting with cellular factors1,2 such as the CtIP polypeptide3,4, a substrate for the ATM (for 'ataxia telangiectasia mutated') protein kinase5. Li et al.6 report that the BRCA1–CtIP interaction is disrupted by ionizing radiation and by other genotoxic stresses that induce phosphorylation of CtIP by ATM kinase, and that this dissociation of the BRCA1–CtIP complex in turn modulates the transcription of DNA-damage-response genes6. We have shown that the BRCA1-binding domain of CtIP (amino-acid residues 133–369) is distal to the sites that are phosphorylated by ATM kinase (residues S664 and S745)7. We now show that the BRCA1–CtIP complex is stable in irradiated cells, and that the phosphorylated isoforms of CtIP that are induced by ionizing radiation still interact in vivo with BRCA1. We conclude that disruption of the BRCA1–CtIP complex cannot account for induction of DNA-damage-response genes in the way proposed by Li et al.6.

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Figure 1: Association of BRCA1 and CtIP in irradiated cells.

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References

  1. Scully, R. & Livingston, D. M. Nature 408, 429–432 (2000).
    Article ADS CAS Google Scholar
  2. Deng, C.-X. & Brodie, S. G. BioEssays 22, 728–737 (2000).
    Article CAS Google Scholar
  3. Yu, X., Wu, L. C., Bowcock, A. M., Aronheim, A. & Baer, R. J. Biol. Chem. 273, 25388–25392 (1998).
    Article CAS Google Scholar
  4. Wong, A. K. et al. Oncogene 17, 2279–2285 (1998).
    Article CAS Google Scholar
  5. Kim, S. T., Lim, D. S., Canman, C. E. & Kastan, M. B. J. Biol. Chem. 274, 37538–37543 (1999).
    Article CAS Google Scholar
  6. Li, S. et al. Nature 406, 210–215 (2000).
    Article ADS CAS Google Scholar
  7. Yu, X. & Baer, R. J. Biol. Chem. 275, 18541–18549 (2000).
    Article CAS Google Scholar
  8. Scully, R. et al. Cell 90, 425–435 (1997).
    Article CAS Google Scholar
  9. Thomas, J. E., Smith, M., Tonkinson, J. L., Rubinfeld, B. & Polakis, P. Cell Growth Differ. 8, 801–809 (1997).
    CAS PubMed Google Scholar
  10. Li, S. et al. J. Biol. Chem. 274, 11334–11338 (1999).
    Article CAS Google Scholar

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Authors and Affiliations

  1. Institute of Cancer Genetics and Department of Pathology, Columbia University College of Physicians and Surgeons, 1150 St Nicholas Avenue, New York, 10032, New York, USA
    Foon Wu-Baer & Richard Baer

Authors

  1. Foon Wu-Baer
  2. Richard Baer

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Correspondence toRichard Baer.

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Wu-Baer, F., Baer, R. Effect of DNA damage on a BRCA1 complex.Nature 414, 36 (2001). https://doi.org/10.1038/35102118

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