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Hsp90–Sgt1 and Skp1 target human Mis12 complexes to ensure efficient formation of kinetochore–microtubule binding sites


The formation of functional kinetochores requires the accurate assembly of a large number of protein complexes. The Hsp90-Sgt1 chaperone complex is important for this process; however, its targets are not conserved and its exact contribution to kinetochore assembly is unclear. Here, we show that human Hsp90-Sgt1 interacts with the Mis12 complex, a so-called keystone complex required to assemble a large fraction of the kinetochore. Inhibition of Hsp90 or Sgt1 destabilizes the Mis12 complex and delays proper chromosome alignment due to inefficient formation of microtubule-binding sites. Interestingly, coinhibition of Sgt1 and the SCF subunit, Skp1, increases Mis12 complexes at kinetochores and restores timely chromosome alignment but forms less-robust microtubule-binding sites. We propose that a balance of Mis12 complex assembly and turnover is required for the efficient and accurate assembly of kinetochore-microtubule binding sites. These findings support a novel role for Hsp90-Sgt1 chaperones in ensuring the fidelity of multiprotein complex assembly.

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