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 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.
Hut
Henderika M J
HM
Department of Radiation and Stress Cell Biology, University of Groningen, UMCG, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Rembacz
Krzysztof P
KP
van Waarde
Maria A W H
MA
Lemstra
Willy
W
van Cappellen
Wiggert A
WA
Kampinga
Harm H
HH
Sibon
Ody C M
OC
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
D000906:Antibodies; D019313:BRCA1 Protein