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Abstract
During mitosis and meiosis, sister chromatid cohesion resists the pulling forces of microtubules, enabling the generation of tension at kinetochores upon chromosome biorientation. How tension is read to signal the bioriented state remains unclear. Shugoshins form a pericentromeric platform that integrates multiple functions to ensure proper chromosome biorientation. Here we show that budding yeast shugoshin Sgo1 dissociates from the pericentromere reversibly in response to tension. The antagonistic activities of the kinetochore-associated Bub1 kinase and the Sgo1-bound phosphatase protein phosphatase 2A (PP2A)-Rts1 underlie a tension-dependent circuitry that enables Sgo1 removal upon sister kinetochore biorientation. Sgo1 dissociation from the pericentromere triggers dissociation of condensin and Aurora B from the centromere, thereby stabilizing the bioriented state. Conversely, forcing sister kinetochores to be under tension during meiosis I leads to premature Sgo1 removal and precocious loss of pericentromeric cohesion. Overall, we show that the pivotal role of shugoshin is to build a platform at the pericentromere that attracts activities that respond to the absence of tension between sister kinetochores. Disassembly of this platform in response to intersister kinetochore tension signals the bioriented state. Therefore, tension sensing by shugoshin is a central mechanism by which the bioriented state is read.
Highlights
For accurate dissemination of the genome, chromosomes are first duplicated during S phase of the cell cycle to generate identical sister chromatids that are held together by cohesion
The protection of pericentromeric cohesin during meiosis I depends on shugoshin, which recruits protein phosphatase 2A associated with its B9-type regulatory subunit (PP2A-B9) to the pericentromere (Kitajima et al 2006; Riedel et al 2006)
We recently found that shugoshins contribute to sister kinetochore biorientation by both enabling the bias to capture by microtubules from opposite poles and engaging the error correction machinery (Verzijlbergen et al 2014)
Summary
For accurate dissemination of the genome, chromosomes are first duplicated during S phase of the cell cycle to generate identical sister chromatids that are held together by cohesion. Shugoshin spatially regulates cohesin loss during mammalian mitosis, where the bulk of cohesin dissociates from chromosome arms during prophase due to the activity of the destabilizing protein Wapl (Waizenegger et al 2000; Hauf et al 2005; Kueng et al 2006; Tang et al 2006; Shintomi and Hirano 2009) In this case, the shugoshin–PP2A-B9 complex dephosphorylates the Wapl-counteracting protein sororin, thereby maintaining its pericentromeric localization (Nishiyama et al 2010; Liu et al 2013b). Biorientation is achieved owing to a bias for sister kinetochores to be captured from opposite poles together with an error correction mechanism that destabilizes incorrect attachments that lack tension (for review, see Tanaka 2010). Overall, Shugoshin acts as an adaptor that attracts multiple activities, including PP2A-B9, CPC, and condensin, to the pericentromere to safeguard accurate chromosome segregation
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