Shugoshin biases chromosomes for biorientation through condensin recruitment to the pericentromere

Abstract

To protect against aneuploidy, chromosomes must attach to microtubules from opposite poles (‘biorientation’) prior to their segregation during mitosis. Biorientation relies on the correction of erroneous attachments by the aurora B kinase, which destabilizes kinetochore-microtubule attachments that lack tension. Incorrect attachments are also avoided because sister kinetochores are intrinsically biased towards capture by microtubules from opposite poles. Here, we show that shugoshin acts as a pericentromeric adaptor that plays dual roles in biorientation in budding yeast. Shugoshin maintains the aurora B kinase at kinetochores that lack tension, thereby engaging the error correction machinery. Shugoshin also recruits the chromosome-organizing complex, condensin, to the pericentromere. Pericentromeric condensin biases sister kinetochores towards capture by microtubules from opposite poles. Our findings uncover the molecular basis of the bias to sister kinetochore capture and expose shugoshin as a pericentromeric hub controlling chromosome biorientation.DOI: http://dx.doi.org/10.7554/eLife.01374.001

Premature Silencing of the Spindle Assembly Checkpoint Is Prevented by the Bub1-H2A-Sgo1-PP2A Axis in Saccharomyces cerevisiae

“…It is unlikely that centromere cohesion prevents SAC silencing, because cohesin mutants show delayed SAC silencing (Biggins and Murray 2001;Jin and Wang 2013). Since some condensin mutants are sensitive to CIK1-CC overexpression (Peplowska et al 2014), another untested possibility is that Sgo1 regulates SAC silencing through condensin; but recent work supports the possibility that the condensin facilitates chromosome biorientation (Verzijlbergen et al 2014). Our results support the notion that Sgo1 recruits PP2A to centromeres to prevent premature SAC silencing.…”

“…Of interest, we noticed that sgo1-N51I mutants exhibited more pronounced viability loss and chromosome missegregation than rts1D mutants after CIK1-CC overexpression. Because PP2A has two regulatory subunits, Rts1 and Cdc55, our explanation is that PP2A Cdc55 and PP2A Rts1 may show redundant function, which is supported by the demonstrated interaction of Sgo1 with both Rts1 and Cdc55 (Verzijlbergen et al 2014). The sgo1-N51I mutation may abolish its interaction with both of them, thereby showing more pronounced phenotypes.…”

“…Centromere-localized Sgo1 recruits PP2A Rts1 , condensin, and Ipl1 kinase complex to the centromere region (Riedel et al 2006;Peplowska et al 2014;Verzijlbergen et al 2014). Although we found that Ipl1 is required to prevent premature SAC silencing in response to tension defects (Jin and Wang 2013), previous work shows that the centromere localization of Ipl1 is dispensable for this function (Campbell and Desai 2013).…”

Sgo1 recruits PP2A to chromosomes to ensure sister chromatid bi-orientation in mitosis

“…Deletion of Sgo1 in budding yeast renders cells unable to respond to a lack of tension between sister chromatids, a hallmark of mis-oriented chromatids (Indjeian et al, 2005;Kitajima et al, 2004;Rabitsch et al, 2004). In yeast and humans, shugoshin recruits the chromosomal passenger complex (CPC) containing the protein kinase Aurora B (Peplowska et al, 2014;Tsukahara et al, 2010;Vanoosthuyse et al, 2007;Verzijlbergen et al, 2014;Yamagishi et al, 2010). In the absence of kinetochore tension, Aurora B phosphorylates multiple substrates at the kinetochore, thereby destabilizing microtubule attachments, and signaling to the spindle assembly checkpoint to delay anaphase until the attachments have been corrected (Lampson and Cheeseman, 2011;Musacchio and Salmon, 2007).…”

“…Aurora B is silenced, and attachments are thereby stabilized, when sister kinetochores are properly attached to microtubules from opposite spindle poles. The ability of shugoshin to recruit the CPC provides a logical explanation for its function in bi-orientation, but it is unclear whether budding yeast Sgo1 works through direct recruitment of the CPC in mitosis (Katis et al, 2004;Kerrebrock et al, 1992;Kitajima et al, 2004;Marston et al, 2004;Storchová et al, 2011;Verzijlbergen et al, 2014) or whether the bi-orientation function of Sgo1 depends in part on its association with PP2A. There is evidence both for and against a role for the isoform of PP2A containing Rts1 (PP2A-Rts1) in budding yeast bi-orientation, and thus the importance of this phosphatase in bi-orientation remains unresolved Peplowska et al, 2014;Verzijlbergen et al, 2014).…”