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Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes

Oncogene volume 24, pages 7619–7623 (2005)Cite this article

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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Author notes

  1. Henderika M J Hut and Krzysztof P Rembacz: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Radiation and Stress Cell Biology, University of Groningen, UMCG, Ant. Deusinglaan 1, 9713 AV, Groningen, The Netherlands

    Henderika M J Hut, Krzysztof P Rembacz, Maria A W H van Waarde, Willy Lemstra, Harm H Kampinga & Ody C M Sibon

  2. Department of Reproduction and Development, Faculty of Medicine and Health Sciences, Erasmus University of Rotterdam, Rotterdam, The Netherlands

    Wiggert A van Cappellen

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  1. Henderika M J Hut
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  2. Krzysztof P Rembacz
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  4. Willy Lemstra
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Correspondence to Ody C M Sibon.

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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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