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 BRCA...

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Veröffentlicht in:Oncogene 2005-11, Vol.24 (51), p.7619-7623
Hauptverfasser: HUT, Henderika M. J, REMBACZ, Krzysztof P, VAN WAARDE, Maria A. W. H, LEMSTRA, Willy, VAN CAPPELLEN, Wiggert A, KAMPINGA, Harm H, SIBON, Ody C. M
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Sprache:eng
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Zusammenfassung: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.
ISSN:0950-9232
1476-5594
DOI:10.1038/sj.onc.1208859