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 G 2M checkpoint regulation. We present evidence that multiple centrosomes can arise in any cell when G2M checkpoint fails and entrance into mitosis occurs in the presence of DNA damage.

Additional Metadata
Keywords BF3, BRCA1, Cancer, Centrosomes, EGFP-BRCA1
Persistent URL dx.doi.org/10.1038/sj.onc.1208859, hdl.handle.net/1765/69956
Journal Oncogene: including Oncogene Reviews
Citation
Hut, H.M.J, Rembacz, K.P, van Waarde, M.A.W.H, Lemstra, W, van Cappellen, W.A, Kampinga, H, & Sibon, O.C.M. (2005). Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes. Oncogene: including Oncogene Reviews, 24(51), 7619–7623. doi:10.1038/sj.onc.1208859