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  • The EMBO Journal (2006) 25, 4033 - 4049
  • doi:10.1038/sj.emboj.7601293

Published online: 24 August 2006



There is a Corrigendum (May 2009) associated with this Article.

The human kinetochore proteins Nnf1R and Mcm21R are required for accurate chromosome segregation

Andrew D McAinsh1,2,5, Patrick Meraldi1,3,5, Viji M Draviam1,5, Alberto Toso3,4 and Peter K Sorger1

  1. Department of Biology, MIT, Cambridge, MA, USA
  2. Chromosome Segregation Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey, UK
  3. Institute of Biochemistry, ETH-Zurich, Zurich, Switzerland
  4. Molecular Life Science, PhD Program, Zurich, Switzerland
  5. These authors contributed equally to this work

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, Chromosome Segregation Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, UK. Tel.: +44 1883 722306; Fax: +44 1883 714375; E-mail: patrick.meraldi@bc.biol.ethz.ch

Received 14 March 2006; Accepted 27 July 2006

Kinetochores (KTs) assemble on centromeric DNA, bi-orient paired sister chromatids on spindle microtubules (MTs) and control cell-cycle progression via the spindle assembly checkpoint. Genetic and biochemical studies in budding yeast have established that three 'linker' complexes, MIND, COMA and NDC80, play essential but distinct roles in KT assembly and chromosome segregation. To determine whether similar linker activities are present at human KTs, we have compared the functions of Nnf1R and Mcm21R, recently identified MIND and COMA subunits, and Nuf2R, a well-characterized NDC80 subunit. We find that the three proteins bind to KTs independent of each other and with distinct cell-cycle profiles. MT–KT attachment is aberrant in Nnf1R- and Mcm21R-depleted cells, whereas it is lost in the absence of Nuf2R. Defective attachments in Nnf1R-depleted cells prevent chromosome congression, whereas those in Mcm21R-depleted cells interfere with spindle assembly. All three human KT proteins are necessary for correct binding of spindle checkpoint proteins to KTs. The differing functions and KT-binding properties of Nnf1R, Mcm21R and Nuf2R suggest that, like their yeast counterparts, the proteins act independent of each other in KT assembly, but that their combined activities are required for checkpoint signaling.

  • Keywords:

    • kinetochore,
    • mitosis,
    • spindle checkpoint