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Abstract
During mitosis, sister chromatids attach to microtubules from opposite poles, called biorientation. Sister chromatid cohesion resists microtubule forces, generating tension, which provides the signal that biorientation has occurred. How tension silences the surveillance pathways that prevent cell cycle progression and correct erroneous kinetochore-microtubule attachments remains unclear. Here we show that SUMOylation dampens error correction to allow stable sister kinetochore biorientation and timely anaphase onset. The Siz1/Siz2 SUMO ligases modify the pericentromere-localized shugoshin (Sgo1) protein before its tension-dependent release from chromatin. Sgo1 SUMOylation reduces its binding to protein phosphatase 2A (PP2A), and weakening of this interaction is important for stable biorientation. Unstable biorientation in SUMO-deficient cells is associated with persistence of the chromosome passenger complex (CPC) at centromeres, and SUMOylation of CPC subunit Bir1 also contributes to timely anaphase onset. We propose that SUMOylation acts in a combinatorial manner to facilitate dismantling of the error correction machinery within pericentromeres and thereby sharpen the metaphase-anaphase transition.
Highlights
Mitosis divides the nucleus to produce two genetically identical daughter cells
Small ubiquitin-like modifier (SUMO) ligases reverse the effects of SGO1 overexpression To identify negative regulators of Sgo1, we screened for high copy suppressors of the poor growth caused by SGO1 overexpression (Clift et al, 2009)
Tethering Sgo1 or Sgo1-K56R K64R K70R K85R (Sgo1-4R) to Rts1 delayed metaphase mildly but significantly (Fig. 9 H). These results demonstrate that SUMO-mediated disruption of the Sgo1–Rts1 interaction is important for stabilizing biorientation and timely anaphase onset
Summary
Mitosis divides the nucleus to produce two genetically identical daughter cells. DNA replication produces sister chromatids, linked together by the cohesin complex. Sister chromatids are aligned at metaphase, allowing spindle microtubules to be captured by kinetochores assembled on centromeres. The correct form of attachment is termed "biorientation," meaning that the kinetochores on the two sister chromatids are attached to microtubules emanating from opposite spindle poles (Tanaka, 2010). Biorientation creates tension, because cohesin holding sister chromatids together resists the pulling force of microtubules. The fulfilment of biorientation allows securin degradation and, activation of the protease separase, which cleaves cohesin, triggering sister chromatid separation (reviewed in Marston [2014])
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