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