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

Banafsheh Etemad, Timo E. F. Kuijt and Geert J. P. L. Kops ()
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Banafsheh Etemad: Hubrecht Institute—KNAW (Royal Netherlands Academy of Arts and Sciences), Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
Timo E. F. Kuijt: Hubrecht Institute—KNAW (Royal Netherlands Academy of Arts and Sciences), Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
Geert J. P. L. Kops: Hubrecht Institute—KNAW (Royal Netherlands Academy of Arts and Sciences), Uppsalalaan 8, 3584 CT Utrecht, The Netherlands

Nature Communications, 2015, vol. 6, issue 1, 1-8

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9987

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