title: Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes.
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.
authors.affiliation: Department of Radiation and Stress Cell Biology, University of Groningen, UMCG, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Henderika M J
authors.initials: HM
authors.lastname: Hut
authors.forename: Krzysztof P
authors.initials: KP
authors.lastname: Rembacz
authors.forename: Maria A W H
authors.initials: MA
authors.lastname: van Waarde
authors.forename: Willy
authors.initials: W
authors.lastname: Lemstra
authors.forename: Wiggert A
authors.initials: WA
authors.lastname: van Cappellen
authors.forename: Harm H
authors.initials: HH
authors.lastname: Kampinga
authors.forename: Ody C M
authors.initials: OC
authors.lastname: Sibon
mesh_terms: D000906:Antibodies; D019313:BRCA1 Protein / Q000235:genetics* / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D018385:Centrosome / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D008938:Mitosis; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology
chemical_list: D000906:Antibodies; D019313:BRCA1 Protein