Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes.

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

doi:10.1038/sj.onc.1208859

PubMed · 16205648

Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes.

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

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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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Antibodies BRCA1 Protein Cell Cycle Centrosome DNA Damage DNA Repair Humans Mitosis Mutation Neoplasms Journal Article Research Support, Non-U.S. Gov't

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Henderika M J Hut, Krzysztof P Rembacz, Maria A W H van Waarde, Willy Lemstra, Wiggert A van Cappellen, Harm H Kampinga, Ody C M Sibon. 2005-11-17. Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes.. https://doi.org/10.1038/sj.onc.1208859

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