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Vol. 14, Issue 5, 1993-2004, May 2003

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Centrosomes Split in the Presence of Impaired DNA Integrity during Mitosis

Henderika M.J. Hut ^*, Willy Lemstra ^*, Engbert H. Blaauw , Gert W.A. van Cappellen , Harm H. Kampinga ^*, and Ody C.M. Sibon ^* 

^* Department of Radiation and Stress Cell Biology, Faculty of Medical Sciences, University of Groningen, 9713 AV Groningen, The Netherlands; Department of Cell Biology and Electron Microscopy, 9713 AV Groningen, The Netherlands; and Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University of Rotterdam, 3000 DR Rotterdam, The Netherlands

Submitted August 16, 2002; Revised November 15, 2002; Accepted January 7, 2003
Monitoring Editor: Tim Stearns

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 -tubulin–GFP and EGFP–-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.

Online version of this article contains video material. Online version of this article is available at www.molbiolcell.org.

Corresponding author. E-mail address: o.c.m.sibon{at}med.rug.nl.

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