Abstract
ABSTRACTUpon establishment of proper kinetochore–microtubule attachment, the spindle assembly checkpoint (SAC) must be silenced to allow onset of anaphase, which is when sister chromatids segregate equally to two daughter cells. However, how proper kinetochore–microtubule attachment leads to timely anaphase onset remains elusive. Furthermore, the molecular mechanisms of chromosome movement during anaphase A remain unclear. In this study, we show that the fission yeast Alp7/TACC protein recruits a protein complex consisting of the kinesin-8 (Klp5–Klp6) and protein phosphatase 1 (PP1) to the kinetochore upon kinetochore–microtubule attachment. Accumulation of this complex at the kinetochore, on the one hand, facilitates SAC inactivation through PP1, and, on the other hand, accelerates polewards chromosome movement driven by the Klp5–Klp6 motor. We identified an alp7 mutant that had specific defects in binding to the Klp5–Klp6–PP1 complex but with normal localisation to the microtubule and kinetochore. Consistent with our proposition, this mutant shows delayed anaphase onset and decelerated chromosome movement during anaphase A. We propose that the recruitment of kinesin-8–PP1 to the kinetochore through Alp7/TACC interaction plays a crucial role in regulation of timely mitotic progression and chromosome movement during anaphase A.
Highlights
During mitosis, the microtubules grow from the opposite spindle poles and bind to the kinetochore, a multi-protein structure found on the centromeric DNA (Cheeseman and Desai, 2008; Takeuchi and Fukagawa, 2012)
These results suggest that deletion of PP1Dis2 in ndc80-NH12 mutant cells suppresses its phenotypes by imposing further mitotic delay, to allow extra time for correction of erroneous kinetochore–microtubule attachment
Deletion of PP1Dis2 was synthetically lethal with ndc80-21, whereas Mad2 deletion had no impact on its temperature sensitivity; it resulted in massive loss of cell viability
Summary
The microtubules grow from the opposite spindle poles and bind to the kinetochore, a multi-protein structure found on the centromeric DNA (Cheeseman and Desai, 2008; Takeuchi and Fukagawa, 2012). Upon establishment of Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, Lincoln’s Inn Fields Laboratories, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK. Received 17 July 2014; Accepted 19 November 2014 proper kinetochore–microtubule attachment, the SAC must be silenced (or deactivated) to allow anaphase onset and segregation of sister chromatids into two daughter cells (Lesage et al, 2011). How PP1 imposes SAC silencing coincident with the establishment of end-on attachment remains unexplored
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