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KNL1-Bubs and RZZ provide two separable pathways for checkpoint activation at human kinetochores
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Silió, Virginia, McAinsh, Andrew D. and Millar, Jonathan B. A. (2015) KNL1-Bubs and RZZ provide two separable pathways for checkpoint activation at human kinetochores. Developmental Cell, 35 (5). pp. 600-613. doi:10.1016/j.devcel.2015.11.012 ISSN 1534-5807.
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Official URL: http://dx.doi.org/10.1016/j.devcel.2015.11.012
Abstract
The spindle assembly checkpoint (SAC) ensures the accurate segregation of sister chromatids during mitosis. Activation of the SAC occurs through a series of ordered molecular events that result in recruitment of Mad1:Mad2 complexes to improperly attached kinetochores. The current model involves sequential phospho-dependent recruitment of Bub3:Bub1 to KNL1 followed by binding of Mad1:Mad2 to Bub1. Here, we show in non-transformed diploid human cells that the KNL1-Bub3-Bub1 (KBB) pathway is required during normal mitotic progression when kinetochores are misaligned but is nonessential for SAC activation and Mad2 loading when kinetochores are unattached from microtubules. We provide evidence that the Rod-ZW10-Zwilch (RZZ) complex is necessary to recruit Mad1:Mad2 to, and delay anaphase onset in response to, unattached kinetochores independently of the KBB pathway. These data suggest that the KBB and RZZ complexes provide two distinct kinetochore receptors for Mad1:Mad2 and reveal mechanistic differences between SAC activation by unattached and improperly attached kinetochores.
| Item Type: | Journal Article | ||||||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Developmental Cell | ||||||||
| Publisher: | Cell Press | ||||||||
| ISSN: | 1534-5807 | ||||||||
| Official Date: | 7 December 2015 | ||||||||
| Dates: |
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| Volume: | 35 | ||||||||
| Number: | 5 | ||||||||
| Page Range: | pp. 600-613 | ||||||||
| DOI: | 10.1016/j.devcel.2015.11.012 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access |
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