Kinetochore-microtubule attachment is sufficient to satisfy the human spindle assembly checkpoint
Etemad, B.; Kuijt, T.E.F.; Kops, G.J.P.L.
(2015) Nature Communications [E], volume 6
(Article)
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
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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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Keywords: binding protein, Article, centromere, chromosome, controlled study, human, human cell, kinetochore microtubule, M phase cell cycle checkpoint, microtubule, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 2041-1723
Publisher: Nature Publishing Group
Note: Export Date: 1 March 2016 Correspondence Address: Kops, G.J.P.L.; Hubrecht Institute-KNAW, Royal Netherlands Academy of Arts and Sciences, Uppsalalaan 8, Netherlands; email: g.kops@hubrecht.eu References: Foley, E.A., Kapoor, T.M., Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore (2013) Nat. Rev. Mol. Cell Biol., 14, pp. 25-37; Sacristan, C., Kops, G.J.P.L., Joined at the hip: Kinetochores, microtubules, and spindle assembly checkpoint signaling (2015) Trends Cell Biol., 25, pp. 21-28; London, N., Biggins, S., Signalling dynamics in the spindle checkpoint response (2014) Nat. Rev. Mol. Cell Biol., 15, pp. 736-747; Nicklas, R.B., Waters, J.C., Salmon, E.D., Ward, S.C., Checkpoint signals in grasshopper meiosis are sensitive to microtubule attachment, but tension is still essential (2001) J. Cell. 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