The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity

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Abstract
Kinetochores are complex protein machines that link chromosomes to spindle microtubules and contain a structural core composed of two conserved protein–protein interaction networks: the well‐characterized KMN (KNL1/MIND/NDC80) and the recently identified CENP‐A NAC/CAD. Here we show that the CENP‐A NAC/CAD subunits can be assigned to one of two different functional classes; depletion of Class I proteins (Mcm21RCENP−O and Fta1RCENP−L) causes a failure in bipolar spindle assembly. In contrast, depletion of Class II proteins (CENP‐H, Chl4RCENP−N, CENP‐I and Sim4RCENP−K) prevents binding of Class I proteins and causes chromosome congression defects, but does not perturb spindle formation. Co‐depletion of Class I and Class II proteins restores spindle bipolarity, suggesting that Class I proteins regulate or counteract the function of Class II proteins. We also demonstrate that CENP‐A NAC/CAD and KMN regulate kinetochore–microtubule attachments independently, even though CENP‐A NAC/CAD can modulate NDC80 levels at kinetochores. Based on our results, we propose that the cooperative action of CENP‐A NAC/CAD subunits and the KMN network drives efficient chromosome segregation and bipolar spindle assembly during mitosis.