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Asymmetric centriole numbers at spindle poles cause chromosome missegregation in cancer

Summary Chromosomal instability is a hallmark of cancer and correlates with the presence of extra centrosomes, which originate from centriole overduplication. Overduplicated centrioles lead to the formation of centriole rosettes, which mature into supernumerary centrosomes in the subsequent cell cyc...

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Hauptverfasser: Cosenza, Marco R. (VerfasserIn) , Cazzola, Anna (VerfasserIn) , Rossberg, Annik (VerfasserIn) , Konotop, Gleb (VerfasserIn) , Bausch, Elena (VerfasserIn) , Slynko, Alla (VerfasserIn) , Holland-Letz, Tim (VerfasserIn) , Raab, Marc-Steffen (VerfasserIn) , Dubash, Taronish Dorab (VerfasserIn) , Glimm, Hanno (VerfasserIn) , Herold-Mende, Christel (VerfasserIn) , Krämer, Alwin (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 22 August 2017
In: Cell reports
Year: 2017, Jahrgang: 20, Heft: 8, Pages: 1906-1920
ISSN:2211-1247
DOI:10.1016/j.celrep.2017.08.005
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1016/j.celrep.2017.08.005
Verlag, kostenfrei, Volltext: http://www.sciencedirect.com/science/article/pii/S2211124717310768
Volltext
Verfasserangaben:Marco R. Cosenza, Anna Cazzola, Annik Rossberg, Nicole L. Schieber, Gleb Konotop, Elena Bausch, Alla Slynko, Tim Holland-Letz, Marc S. Raab, Taronish Dubash, Hanno Glimm, Sven Poppelreuther, Christel Herold-Mende, Yannick Schwab and Alwin Krämer
Beschreibung
Zusammenfassung:Summary Chromosomal instability is a hallmark of cancer and correlates with the presence of extra centrosomes, which originate from centriole overduplication. Overduplicated centrioles lead to the formation of centriole rosettes, which mature into supernumerary centrosomes in the subsequent cell cycle. While extra centrosomes promote chromosome missegregation by clustering into pseudo-bipolar spindles, the contribution of centriole rosettes to chromosome missegregation is unknown. We used multi-modal imaging of cells with conditional centriole overduplication to show that mitotic rosettes in bipolar spindles frequently harbor unequal centriole numbers, leading to biased chromosome capture that favors binding to the prominent pole. This results in chromosome missegregation and aneuploidy. Rosette mitoses lead to viable offspring and significantly contribute to progeny production. We further show that centrosome abnormalities in primary human malignancies frequently consist of centriole rosettes. As asymmetric centriole rosettes generate mitotic errors that can be propagated, rosette mitoses are sufficient to cause chromosome missegregation in cancer.
Beschreibung:Gesehen am 27.09.2018
Beschreibung:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2017.08.005

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