Centrosomes split in the presence of impaired DNA integrity during mitosis

HMJ Hut, W Lemstra, EH Blaauw, GWA van Cappellen, HH Kampinga, OCM Sibon*

*Corresponding author for this work

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    Abstract

    A well-established function of centrosomes is their role in accomplishing a successful mitosis that gives rise to a pair of identical daughter cells. We recently showed that DNA replication defects and DNA damage in Drosophila embryos trigger centrosomal changes, but it remained unclear whether comparable centrosomal responses can be provoked in somatic mammalian cells. To investigate the centrosomal organization in the presence of impaired DNA integrity, live and ultrastructural analysis was performed on gamma-tubulin-GFP and EGFP-alpha-tubulin- expressing Chinese hamster ovary cells. We have shown that during mitosis in the presence of incompletely replicated or damaged DNA, centrosomes split into fractions containing only one centriole. This results in the formation of multipolar spindles with extra centrosome-like structures. Despite the extra centrosomes and the multipolarity of the spindles, cells do exit from mitosis, resulting in severe division errors. Our data provide evidence of a novel mechanism showing how numerous centrosomes and spindle defects can arise and how this can lead to the formation of aneuploid cells.

    Original languageEnglish
    Pages (from-to)1993-2004
    Number of pages12
    JournalMolecular Biology of the Cell
    Volume14
    Issue number5
    DOIs
    Publication statusPublished - May-2003

    Keywords

    • CHINESE-HAMSTER OVARY
    • CELL-CYCLE PROGRESSION
    • DUPLICATION CYCLE
    • GAMMA-TUBULIN
    • CHROMOSOME SEGREGATION
    • PROTEIN-KINASE
    • AMPLIFICATION
    • PHOSPHATASE
    • DROSOPHILA
    • SPINDLE

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