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Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes

Abstract

A remarkable and yet unexplained phenomenon in cancer cells is the presence of multiple centrosomes, organelles required for normal cell division. Previously, it was demonstrated that the tumor suppressor BRCA1 is a component of centrosomes. This observation led to the hypothesis that defective BRCA1 results in malfunctioning centrosomes and faulty centrosomes are a possible cause of cancer. Using EGFP-tagged fusion proteins and BRCA1−/− cells we show that although some BRCA1 antibodies do label centrosomes under certain fixation conditions, BRCA1 is not a centrosomal protein. Therefore, it is unlikely that a mutation in BRCA1 directly alters centrosome structure and function. BRCA1 plays an established role in DNA damage repair and in G2/M checkpoint regulation. We present evidence that multiple centrosomes can arise in any cell when G2/M checkpoint fails and entrance into mitosis occurs in the presence of DNA damage.

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Acknowledgements

This work was supported by grants from the Netherlands Organization for Scientific Research: NWO (901-01-221), and from the Interuniversitary Institute for Radiopathology and Radiation Protection: IRS (7.2.6).

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Correspondence to Ody C M Sibon.

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Supplemenatry Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

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Hut, H., Rembacz, K., van Waarde, M. et al. Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes. Oncogene 24, 7619–7623 (2005). https://doi.org/10.1038/sj.onc.1208859

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  • DOI: https://doi.org/10.1038/sj.onc.1208859

Keywords

  • BRCA1
  • EGFP-BRCA1
  • BF3
  • cancer
  • centrosomes

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