Mph1 kinetochore localization is crucial and upstream in the hierarchy of spindle assembly checkpoint protein recruitment to kinetochores

Advance Online Publication July 23, 2012 doi: 10.1242/?jcs.110387 The spindle assembly checkpoint (SAC) blocks entry into anaphase until all chromosomes have stably attached to the mitotic spindle through their kinetochores. The checkpoint signal originates from unattached kinetochores, where SAC proteins enrich. Whether the enrichment of all SAC proteins is crucial for SAC signalling is unclear. Here we provide evidence that in fission yeast, recruitment of the kinase Mph1 is of vital importance for a stable SAC arrest. An Mph1 mutant that eliminates kinetochore enrichment abolishes SAC signalling, whereas forced recruitment of this mutant to kinetochores restores SAC signalling. In bub3? cells, the SAC is functional with only Mph1 and the Aurora kinase Ark1, but no other SAC proteins, enriched at kinetochores. We analysed the network of dependencies for SAC protein localization to kinetochores and identify a three-layered hierarchy with Ark1 and Mph1 on top, Bub1 and Bub3 in the middle, and Mad3 as well as the Mad1-Mad2 complex at the lower end of the hierarchy. If Mph1 is artificially recruited to kinetochores, Ark1 becomes dispensable for SAC activity. Our results highlight the critical role of Mph1 at kinetochores and suggest that the Mad1-Mad2 complex does not necessarily need to enrich at kinetochores for functional SAC signalling.

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