Fin1-PP1 Helps Clear Spindle Assembly Checkpoint Protein Bub1 from Kinetochores in Anaphase.
Fin1-PP1 Helps Clear Spindle Assembly Checkpoint Protein Bub1 from Kinetochores in Anaphase.
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DOI：
10.1016/j.celrep.2016.01.007
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发表时间：
2016-02-09
期刊：
影响因子：
8.8
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Bokros M;Gravenmier C;Jin F;Richmond D;Wang Y
纺锤体组装检查点 (SAC) 监测染色体附着缺陷，动粒处 SAC 蛋白的组装对于其激活至关重要，但 SAC 分解过程仍然未知。我们发现，删除 14-3-3 蛋白 Bmh1 或过度激活 FEAR（Cdc14 早期后期释放）会导致芽殖酵母中的 SAC 过早沉默，这取决于动粒蛋白 Fin1 与蛋白磷酸酶 PP1 形成复合物。先前的研究表明，FEAR 依赖性 Fin1 去磷酸化会促进 Bmh1-Fin1 解离，从而使着丝粒招募 Fin1-PP1。我们发现进入后期后 fin1Δ 突变体中 SAC 蛋白 Bub1 存在持续的着丝粒关联。因此，我们揭示了一种从动粒中清除 SAC 蛋白的机制。进入后期后，FEAR 激活促进 Fin1-PP1 着丝粒富集，导致着丝粒处 SAC 解体。这种机制是 SAC 受到攻击后有效 SAC 沉默所必需的，不合时宜的 Fin1-着丝粒关联会导致过早的 SAC 沉默和染色体错误分离。
The 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 hyper-activation of FEAR (Cdc14 Early Anaphase Release) 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 being challenged, and untimely Fin1-kinetochore association causes premature SAC silencing and chromosome missegregation.