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Multipolar mitosis of tetraploid cells: inhibition by p53 and dependency on Mos
Author(s) -
Vitale Ilio,
Senovilla Laura,
Jemaà Mohamed,
Michaud Mickaël,
Galluzzi Lorenzo,
Kepp Oliver,
Nanty Lisa,
Criollo Alfredo,
RelloVarona Santiago,
Manic Gwenola,
Métivier Didier,
Vivet Sonia,
Tajeddine Nicolas,
Joza Nicholas,
Valent Alexander,
Castedo Maria,
Kroemer Guido
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.11
Subject(s) - biology , mitosis , microbiology and biotechnology , dependency (uml) , genetics , engineering , systems engineering
Tetraploidy can constitute a metastable intermediate between normal diploidy and oncogenic aneuploidy. Here, we show that the absence of p53 is not only permissive for the survival but also for multipolar asymmetric divisions of tetraploid cells, which lead to the generation of aneuploid cells with a near‐to‐diploid chromosome content. Multipolar mitoses (which reduce the tetraploid genome to a sub‐tetraploid state) are more frequent when p53 is downregulated and the product of the Mos oncogene is upregulated. Mos inhibits the coalescence of supernumerary centrosomes that allow for normal bipolar mitoses of tetraploid cells. In the absence of p53, Mos knockdown prevents multipolar mitoses and exerts genome‐stabilizing effects. These results elucidate the mechanisms through which asymmetric cell division drives chromosomal instability in tetraploid cells.