SUMOylation stabilizes sister kinetochore biorientation to allow timely anaphase |
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Authors: | Xue Bessie Su,Menglu Wang,Claudia Schaffner,Olga O. Nerusheva,Dean Clift,Christos Spanos,David A. Kelly,Michael Tatham,Andreas Wallek,Yehui Wu,Juri Rappsilber,A. Arockia Jeyaprakash,Zuzana Storchova,Ronald T. Hay,Adè le L. Marston |
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Affiliation: | 1.Wellcome Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, UK;2.Laboratory of Molecular Biology, Medical Research Council, Cambridge, UK;3.Centre for Gene Regulation and Expression, University of Dundee, Dundee, UK;4.Max Planck Institute of Biochemistry, Martinsried, Germany;5.Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany;6.Technische Universität Kaiserslautern, Kaiserslautern, Germany |
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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. |
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