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The CENP‐A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity
Author(s) -
McClelland Sarah E,
Borusu Satyarebala,
Amaro Ana C,
Winter Jennifer R,
Belwal Mukta,
McAinsh Andrew D,
Meraldi Patrick
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601927
Subject(s) - biology , kinetochore , cad , microbiology and biotechnology , genetics , chromosome , biochemistry , gene
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 (Mcm21R CENP−O and Fta1R CENP−L ) causes a failure in bipolar spindle assembly. In contrast, depletion of Class II proteins (CENP‐H, Chl4R CENP−N , CENP‐I and Sim4R CENP−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.