Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes

HMJ Hut, KP Rembacz, MAWH van Waarde, W Lemstra, WA van Cappellen, HH Kampinga, OCM Sibon*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    15 Citations (Scopus)

    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. xation 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 G(2)/M checkpoint regulation. We present evidence that multiple centrosomes can arise in any cell when G(2)/M checkpoint fails and entrance into mitosis occurs in the presence of DNA damage.

    Original languageEnglish
    Pages (from-to)7619-7623
    Number of pages5
    JournalONCOGENE
    Volume24
    Issue number51
    DOIs
    Publication statusPublished - 17-Nov-2005

    Keywords

    • BRCA1
    • EGFP
    • BF3
    • cancer
    • centrosomes
    • DNA-DAMAGE
    • AMPLIFICATION
    • CELLS
    • DUPLICATION
    • INSTABILITY
    • INTEGRITY
    • MITOSIS

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