Article
- The EMBO Journal (2007) 26, 5033 - 5047
- doi:10.1038/sj.emboj.7601927
Published online: 15 November 2007
Subject Categories:
The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity
Sarah E McClelland1,a, Satyarebala Borusu2,3,a, Ana C Amaro2,3, Jennifer R Winter1, Mukta Belwal2,3, Andrew D McAinsh1 and Patrick Meraldi2
- Chromosome Segregation Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey, UK
- Institute of Biochemistry, ETH Zurich, Zurich, Switzerland
- Molecular Life Sciences PhD Program, Zurich, Switzerland
Correspondence to:
Andrew D McAinsh, Chromosome Segregation Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, UK. Tel.: +44 1883 722306; Fax: +44 1883 714375; E-mail: a.mcainsh@mcri.ac.uk
Patrick Meraldi, Institute of Biochemistry, ETH Zurich, Zurich 8093, Switzerland. Tel.: +41 44 632 63 47; Fax: +41 44 632 12 69; E-mail: patrick.meraldi@bc.biol.ethz.ch
aThese authors contributed equally to this work
Received 21 September 2007; Accepted 24 October 2007
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.
Keywords:
- CENP-H,
- FtalR,
- Mcm21R,
- mitosis,
- spindle
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