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Spindle Multipolarity Is Prevented by Centrosomal Clustering
Nicholas J. Quintyne,1
Janet E. Reing,1
Diane R. Hoffelder,1
Susanne M. Gollin,2
William S. Saunders1*
Abstract:
Most tumor cells are characterized by increased genomic instabilityand chromosome segregational defects, often associated withhyperamplification of the centrosome and the formation of multipolarspindles. However, extra centrosomes do not always lead to multipolarity.Here, we describe a process of centrosomal clustering that preventedthe formation of multipolar spindles in noncancer cells. Noncancercells needed to overcome this clustering mechanism to allowmultipolar spindles to form at a high frequency. The microtubulemotor cytoplasmic dynein was a critical part of this coalescingmachinery, and in some tumor cells overexpression of the spindleprotein NuMA interfered with dynein localization, promotingmultipolarity.
1 Department of Biological Sciences, 2 Department of Human Genetics and the University of Pittsburgh Cancer Institute, University of Pittsburgh, 4249 Fifth Avenue, Pittsburgh, PA 15260, USA.
* To whom correspondence should be addressed. E-mail: wsaund{at}pitt.edu
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