Article ID Journal Published Year Pages File Type
2040524 Cell Reports 2016 12 Pages PDF
Abstract

•bmh1 deletion or hyperactive FEAR leads to Fin1-mediated premature SAC silencing•Bmh1 and FEAR regulate Fin1 kinetochore localization•Untimely kinetochore localization of Fin1-PP1 causes premature SAC silencing•Fin1 promotes dissociation of SAC protein Bub1 from kinetochores in anaphase

SummaryThe spindle assembly checkpoint (SAC) monitors chromosome attachment defects, and the assembly of SAC proteins at kinetochores is essential for its activation, but the SAC disassembly process remains unknown. We found that deletion of a 14-3-3 protein, Bmh1, or hyperactivation of Cdc14 early anaphase release (FEAR) allows premature SAC silencing in budding yeast, which depends on a kinetochore protein Fin1 that forms a complex with protein phosphatase PP1. Previous works suggest that FEAR-dependent Fin1 dephosphorylation promotes Bmh1-Fin1 dissociation, which enables kinetochore recruitment of Fin1-PP1. We found persistent kinetochore association of SAC protein Bub1 in fin1Δ mutants after anaphase entry. Therefore, we revealed a mechanism that clears SAC proteins from kinetochores. After anaphase entry, FEAR activation promotes kinetochore enrichment of Fin1-PP1, resulting in SAC disassembly at kinetochores. This mechanism is required for efficient SAC silencing after SAC is challenged, and untimely Fin1-kinetochore association causes premature SAC silencing and chromosome missegregation.

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