TY  - JOUR
AU  - Cosenza, Marco Raffaele
AU  - Cazzola, Anna
AU  - Rossberg, Annik
AU  - Schieber, Nicole L
AU  - Konotop, Gleb
AU  - Bausch, Elena
AU  - Slynko, Alla
AU  - Holland-Letz, Tim
AU  - Raab, Marc-Steffen
AU  - Dubash, Taronish Dorab
AU  - Glimm, Hanno
AU  - Poppelreuther, Sven
AU  - Herold-Mende, Christel
AU  - Schwab, Yannick
AU  - Krämer, Alwin
TI  - Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in Cancer.
JO  - Cell reports
VL  - 20
IS  - 8
SN  - 2211-1247
CY  - Maryland Heights, MO
PB  - Cell Press
M1  - DKFZ-2017-04037
SP  - 1906 - 1920
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28834753
DO  - DOI:10.1016/j.celrep.2017.08.005
UR  - https://inrepo02.dkfz.de/record/128015
ER  -