Aneuploidy-chromosome instability leading to incorrect chromosome number in dividing cells-can arise from defects in centrosome duplication, bipolar spindle formation, kinetochore-microtubule attachment, chromatid cohesion, mitotic checkpoint monitoring or cytokinesis. As most tumours show some degree of aneuploidy, mechanistic understanding of these pathways has been an intense area of researc...

Accurate chromosome segregation relies on the bipolar mitotic spindle. In many eukaryotes, spindle formation is driven by the plus-end-directed motor kinesin-5 that generates outward force to establish spindle bipolarity. Its inhibition leads to the emergence of monopolar spindles with mitotic arrest. Intriguingly, simultaneous inactivation of the minus-end-directed motor kinesin-14 restores sp...

We isolated a cDNA clone encoding a kinesin-related protein, which we named XKCM1. Antibodies to XKCM1 stain mitotic centromeres and spindle poles. Immunodepletion and antibody addition experiments in an in vitro spindle assembly assay show that XKCM1 is required for both establishment and maintenance of mitotic spindles. The structures that form in the absence of XKCM1 contain abnormally long ...

In most species, oocytes lack centrosomes. Accurate meiotic spindle assembly and chromosome segregation - essential to prevent miscarriage or developmental defects - thus occur through atypical mechanisms that are not well characterized. Using quantitative in vitro and in vivo functional assays in the C. elegans oocyte, we provide novel evidence that the kinesin-13 KLP-7 promotes destabilizatio...

The central spindle regulates cleavage furrow formation and cytokinesis and is composed of antiparallel microtubules bundled by microtubule-associated proteins and kinesin motors. One key protein in the central spindle is a Rho family GTPase-activating protein, CYK-4/MgcRacGAP, whose target is the subject of two new studies that arrive at divergent models.

Microtubules within meiotic and mitotic spindles continually move towards spindle poles in a process termed poleward flux, which is essential for spindle integrity and faithful chromosome segregation. Kinesin 5 is a longstanding candidate for a molecular motor that might drive poleward flux, and has been shown to drive flux and to be necessary for spindle bipolarity in Xenopus egg extracts. How...

Kinesin motors play central roles in bipolar spindle assembly. In many eukaryotes, spindle pole separation is driven by Kinesin-5 that generates outward force. This outward force is balanced by antagonistic inward force elicited by Kinesin-14 and/or Dynein. In fission yeast, two Kinesin-14s, Pkl1 and Klp2, play an opposing role against Kinesin-5/Cut7. However, how these two Kinesin-14s coordina...

BACKGROUND The pole-to-pole distance of the metaphase spindle is reasonably constant in a given cell type; in the case of vertebrate female oocytes, this steady-state length can be maintained for substantial lengths of time, during which time microtubules remain highly dynamic. Although a number of molecular perturbations have been shown to influence spindle length, a global understanding of th...

We identified the mitotic kinesin-like protein 2 (MKlp2), a kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis, as a target of the mitotic checkpoint protein Mad2. MKlp2 possesses a consensus Mad2-binding motif required for Mad2 binding. Mad2 prevents MKlp2 from loading onto the mitotic spindle, a prerequisite step for its function as a mitotic kinesin. Furthermore, Ma...

The microtubule spindle apparatus dictates the plane of cell cleavage in animal cells. During development, dividing cells control the position of the spindle to determine the size, location, and fate of daughter cells. Spindle positioning depends on pulling forces that act between the cell periphery and astral microtubules. This involves dynein recruitment to the cell cortex by a heterotrimeric...