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Shugoshin 1 Plays a Central Role in Kinetochore Assembly and is Required for Kinetochore Targeting of Plk1

Jeroen Pouwels, Anu M. Kukkonen, Weijie Lan, John R. Daum, Gary J. Gorbsky, P. Todd Stukenberg and Marko J. Kallio

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Physical connection between the sister chromatids is mediated by the cohesin protein complex. During prophase, cohesin is removed from the chromosome arms while the centromeres remain united. Shugoshin1 (Sgo1) is required for maintenance of centromeric cohesion from prophase to the metaphase-anaphase transition. Furthermore, Sgo1 has been proposed to regulate kinetochore microtubule stability and sense interkinetochore tension, two tasks which are tightly coupled with the function of the Chromosomal Passenger Complex (CPC) and Polo-like kinase 1 (Plk1). Here we show that depletion or chemical inhibition of Aurora B kinase (AurB), the catalytic subunit of the CPC, disrupts accumulation of Sgo1 on the kinetochores in HeLa cells and causes Sgo1 to localize on the chromosome arms. RNAi assays show that depletion of Sgo1 did not affect AurB localization but diminished Plk1 kinetochore binding. Furthermore, we demonstrate that vertebrate Sgo1 is phosphorylated by both AurB and Plk1 in vitro. The data presented here includes an extensive analysis of kinetochore targeting interdependencies of mitotic proteins that propose a novel branch in kinetochore assembly where Sgo1 and Plk1 have central roles. Furthermore our studies implicate Sgo1 in the tension sensing mechanism of the spindle checkpoint by regulating Plk1 kinetochore affinity.

Authors

Jeroen Pouwels

VTT Technical Research Centre of Finland; Turku, Finland

Anu M. Kukkonen

VTT Technical Research Centre of Finland; Turku, Finland

Weijie Lan

University of Virginia Medical School; Charlottesville, Virginia

John R. Daum

Oklahoma Medical Research Foundation; Oklahoma City, Oklahoma

Gary J. Gorbsky

Oklahoma Medical Research Foundation

P. Todd Stukenberg

University of Virginia School of Medicine Charlottesville

Marko J. Kallio

VTT Technical Research Centre of Finland; Turku, Finland

Purchase article for $19

Subscribe to this journal for $129/year