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The spindle checkpoint protects against aneuploidy by ensuring that dividing cells only proceed with chromosome segregation once all kinetochores are stably attached to spindle microtubules. The checkpoint protein MAD1 localizes to the corona, a structural expansion of the kinetochore forming in the absence of microtubule attachment, but molecular mechanism or functional significance of this localization remains unknown. Recent results now show that cyclin B1 recruits MAD1 to the corona and that this MAD1 pool is required for robust checkpoint signaling. [ABSTRACT FROM AUTHOR]

Maintenance of genomic stability during eukaryotic cell division relies on the spindle assembly checkpoint (SAC) that prevents mitotic exit until all chromosomes are properly attached to the spindle. Polo is a mitotic kinase proposed to be involved in SAC function, but its role has remained elusive. We demonstrate that Polo and Aurora B functional interdependency comprises a positive feedback loop that promotes Mps1 kinetochore localization and activity. Expression of constitutively active Polo restores normal Mps1 kinetochore levels even after Aurora B inhibition, highlighting a role for Polo in Mps1 recruitment to unattached kinetochores downstream of Aurora B. We also show that Mps1 kinetochore localization is required for BubR1 hyperphosphorylation and formation of the 3F3/2 phosphoepitope. This is essential to allow recruitment of Cdc20 to unattached kinetochores and the assembly of anaphase-promoting complex/cyclosome-inhibitory complexes to levels that ensure long-term SAC activity. We propose a model in which Polo controls Mps1-dependent BubR1 phosphorylation to promote Cdc20 kinetochore recruitment and sustained SAC function. [ABSTRACT FROM AUTHOR]

Accurate chromosome segregation in mitosis requires sister kinetochores to bind to microtubules from opposite spindle poles. The stability of kinetochore–microtubule attachments is fine‐tuned to prevent or correct erroneous attachments while preserving amphitelic interactions. Polo kinase has been implicated in both stabilizing and destabilizing kinetochore–microtubule attachments. However, the mechanism underlying Polo–destabilizing activity remains elusive. Here, resorting to an RNAi screen in Drosophila for suppressors of a constitutively active Polo mutant, we identified a strong genetic interaction between Polo and the Rod–ZW10–Zwilch (RZZ) complex, whose kinetochore accumulation has been shown to antagonize microtubule stability. We find that Polo phosphorylates Spindly and impairs its ability to bind to Zwilch. This precludes dynein‐mediated removal of the RZZ from kinetochores and consequently delays the formation of stable end‐on attachments. We propose that high Polo‐kinase activity following mitotic entry directs the RZZ complex to minimize premature stabilization of erroneous attachments, whereas a decrease in active Polo in later mitotic stages allows the formation of stable amphitelic spindle attachments. Our findings demonstrate that Polo tightly regulates the RZZ–Spindly–dynein module during mitosis to ensure the fidelity of chromosome segregation. Synopsis: Polo kinase is involved in both stabilizing and destabilizing kinetochore‐microtubule attachments during mitosis. A Drosophila RNAi screen identifies the RZZ complex as mediator of Polo‐dependent destabilization of early mitotic spindle mis‐attachments. Constitutively‐active Polo kinase delays formation of stable end‐on kinetochore‐microtubule attachments in an RZZ‐dependent manner.Polo phosphorylates the dynein adaptor Spindly at prometaphase kinetochores, decreasing its affinity towards the RZZ complex.Dynein promptly strips phosphorylated Spindly from kinetochores, leaving the RZZ behind to reduce the stability of microtubule attachments.Decreasing Spindly phosphorylation as chromosomes congress enables efficient dynein‐mediated removal of RZZ from kinetochores and consequent stabilization of microtubule attachments.Preventing Polo from phosphorylating Spindly during early mitosis leads to premature stabilization of merotelic attachments. [ABSTRACT FROM AUTHOR]