Kinetochore-microtubule attachment is sufficient to satisfy the human spindle assembly checkpoint

Nat Commun. 2015 Dec 1;6:8987. doi: 10.1038/ncomms9987.

Abstract

The spindle assembly checkpoint (SAC) is a genome surveillance mechanism that protects against aneuploidization. Despite profound progress on understanding mechanisms of its activation, it remains unknown what aspect of chromosome-spindle interactions is monitored by the SAC: kinetochore-microtubule attachment or the force generated by dynamic microtubules that signals stable biorientation of chromosomes? To answer this, we uncoupled these two processes by expressing a non-phosphorylatable version of the main microtubule-binding protein at kinetochores (HEC1-9A), causing stabilization of incorrect kinetochore-microtubule attachments despite persistent activity of the error-correction machinery. The SAC is fully functional in HEC1-9A-expressing cells, yet cells in which chromosomes cannot biorient but are stably attached to microtubules satisfy the SAC and exit mitosis. SAC satisfaction requires neither intra-kinetochore stretching nor dynamic microtubules. Our findings support the hypothesis that in human cells the end-on interactions of microtubules with kinetochores are sufficient to satisfy the SAC without the need for microtubule-based pulling forces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Segregation
  • Cytoskeletal Proteins
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • M Phase Cell Cycle Checkpoints*
  • Microtubules / metabolism*
  • Mitosis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Spindle Apparatus / metabolism*

Substances

  • Cytoskeletal Proteins
  • NDC80 protein, human
  • Nuclear Proteins