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  • Title: Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes.
    Author: Hut HM, Rembacz KP, van Waarde MA, Lemstra W, van Cappellen WA, Kampinga HH, Sibon OC.
    Journal: Oncogene; 2005 Nov 17; 24(51):7619-23. PubMed ID: 16205648.
    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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