Synchronizing chromosome segregation by flux-dependent force equalization at kinetochores.
The synchronous movement of chromosomes during anaphase ensures their correct inheritance in every cell division. This reflects the uniformity of spindle forces acting on chromosomes and their simultaneous entry into anaphase. Although anaphase onset is controlled by the spindle assembly checkpoint, it remains unknown how spindle forces are uniformly distributed among different chromosomes. In this paper, we show that tension uniformity at metaphase kinetochores and subsequent anaphase synchrony in Drosophila S2 cells are promoted by spindle microtubule flux. These results can be explained by a mechanical model of the spindle where microtubule poleward translocation events associated with flux reflect relaxation of the kinetochore-microtubule interface, which accounts for the redistribution and convergence of kinetochore tensions in a timescale comparable to typical metaphase duration. As predicted by the model, experimental acceleration of mitosis precludes tension equalization and anaphase synchrony. We propose that flux-dependent equalization of kinetochore tensions ensures a timely and uniform maturation of kinetochore-microtubule interfaces necessary for error-free and coordinated segregation of chromosomes in anaphase.
Matos
Irina
I
Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Pereira
António J
AJ
Lince-Faria
Mariana
M
Cameron
Lisa A
LA
Salmon
Edward D
ED
Maiato
Helder
H
D000705:Anaphase; D000818:Animals; D001696:Biomechanical Phenomena; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D020090:Chromosome Segregation; D002875:Chromosomes / Q000378:metabolism; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D008677:Metaphase; D008866:Microsurgery; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D010641:Phenotype; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism
D029721:Drosophila Proteins