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

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作者：
Banafsheh Etemad
Timo E. F. Kuijt
Geert J. P. L. Kops
机构：
[1] Hubrecht Institute—KNAW (Royal Netherlands Academy of Arts and Sciences),
[2] Uppsalalaan 8,undefined
[3] 3584 CT Utrecht,undefined
[4] The Netherlands,undefined
[5] Molecular Cancer Research,undefined
[6] University Medical Center Utrecht,undefined
[7] Center for Molecular Medicine,undefined
[8] University Medical Center Utrecht,undefined
[9] Cancer Genomics Netherlands,undefined
[10] University Medical Center Utrecht,undefined
来源：
Nature Communications | / 6卷
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摘要：
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.
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