Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes
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.
|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|
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