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Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 59356
Author(s) Meraldi, P; Honda, R; Nigg, EA
Author(s) at UniBasel Nigg, Erich
Year 2002
Title Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells
Journal The EMBO journal
Volume 21
Number 4
Pages / Article-Number 483-492
Keywords cancer, cell cycle, chromosomal instability, centrosome anomalies
Abstract

Aberrations in centrosome numbers have long been implicated in aneuploidy and tumorigenesis, but their origins are unknown. Here we have examined how overexpression of Aurora-A kinase causes centrosome amplification in cultured cells. We show that excess Aurora-A does not deregulate centrosome duplication but gives rise to extra centrosomes through defects in cell division and consequent tetraploidization. Over expression of other mitotic kinases (Polo-like kinase 1 and Aurora-B) also causes multinucleation and concomitant increases in centrosome numbers. Absence of a p53 checkpoint exacerbates this phenotype, providing a plausible explanation for the centrosome amplification typical of p53-/- cells. We propose that errors during cell division, combined with the inability to detect the resulting hyperploidy, constitute a major cause for numerical centrosome aberrations in tumors.

Publisher Nature Publishing Group
ISSN/ISBN 0261-4189
edoc-URL http://edoc.unibas.ch/dok/A5249411
Full Text on edoc No
Digital Object Identifier DOI 10.1093/emboj/21.4.483
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/11847097
ISI-Number WOS:000174014700001
Document type (ISI) Article
 
   

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