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PMID: 12802070 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Centrosomes split in the presence of impaired DNA integrity during mitosis.

Molecular biology of the cell ·Vol. 14 ·No. 5 ·2003-05-00 ·Pages 1993-2004

Hut HM, Lemstra W, Blaauw EH, Van Cappellen GW, Kampinga HH, Sibon OC

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.

MeSH Terms
Actins/metabolism Animals CHO Cells Centrosome/metabolism Cricetinae DNA/metabolism Mitosis/physiology Spindle Apparatus/physiology
Chemicals
Actins DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hut Henderika M J
Department of Radiation and Stress Cell Biology, Faculty of Medical Sciences, University of Groningen, The Netherlands.
Lemstra Willy
Blaauw Engbert H
Van Cappellen Gert W A
Kampinga Harm H
Sibon Ody C M
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e02-08-0510
Published
2003-05-00
Epub
2003-00-06
Pages
1993-2004
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC165092
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e02-08-0510 PMC Full Text View journal details
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