BUB-1 promotes amphitelic chromosome biorientation via multiple activities at the kinetochore
Abstract
Accurate chromosome segregation relies on bioriented amphitelic attachments of chromosomes to microtubules of the mitotic spindle, in which sister chromatids are connected to opposite spindle poles. BUB-1 is a protein of the Spindle Assembly Checkpoint (SAC) that coordinates chromosome attachment with anaphase onset. BUB-1 is also required for accurate sister chromatid segregation independently of its SAC function, but the underlying mechanism remains unclear. Here we show that, in Caenorhabditis elegans embryos, BUB-1 accelerates the establishment of non-merotelic end-on kinetochore-microtubule attachments by recruiting the RZZ complex and its downstream partner dynein-dynactin at the kinetochore. In parallel, BUB-1 limits attachment maturation by the SKA complex. This activity opposes kinetochore-microtubule attachment stabilisation promoted by CLS-2CLASP-dependent kinetochore-microtubule assembly. BUB-1 is therefore a SAC component that coordinates the function of multiple downstream kinetochore-associated proteins to ensure accurate chromosome segregation.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Fondation ARC pour la Recherche sur le Cancer (Doctorant en 4e année de thèse)
- Frances Edwards
Fondation pour la Recherche Médicale (DEQ20160334869)
- Julien Dumont
National Institutes of Health (R01GM117407)
- Julie C Canman
Mairie de Paris (Emergence)
- Julien Dumont
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jon Pines, Institute of Cancer Research Research, United Kingdom
Version history
- Received: August 1, 2018
- Accepted: December 13, 2018
- Accepted Manuscript published: December 14, 2018 (version 1)
- Version of Record published: December 21, 2018 (version 2)
- Version of Record updated: March 8, 2019 (version 3)
Copyright
© 2018, Edwards et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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