Checkpoint Proteins Bub1 and Bub3 Delay Anaphase Onset in Response to Low Tension Independent of Microtubule-Kinetochore Detachment
Checkpoint Proteins Bub1 and Bub3 Delay Anaphase Onset in Response to Low Tension Independent of Microtubule-Kinetochore Detachment
复制标题
DOI：
10.1016/j.celrep.2019.03.027
复制
发表时间：
2019-04-09
期刊：
影响因子：
8.8
通讯作者：
Gupta, Mohan L., Jr.
中科院分区：
文献类型：
--
作者：
Proudfoot, Kathleen G.;Anderson, Samuel J.;Gupta, Mohan L., Jr.
纺锤体组装检查点（SAC）延迟后期开始，直到姐妹染色体结合到微管从相反的纺锤体极。只有这样，动态微管才能在姐妹动粒之间产生张力。动粒附着和张力的相互依赖性已经证明对理解SAC机制具有挑战性。SAC是否仅仅对动粒附着或紧张状态作出反应仍然不清楚。与高等真核生物不同，芽殖酵母动粒仅结合一个微管，简化了附着和张力之间的关系。我们开发了一个紫杉醇敏感的酵母模型，以减少张力完全组装的纺锤体。我们的研究结果表明，低张力双极附着动粒延迟后期发病，独立的分离。相对于由未附着的动粒施加的延迟，延迟是短暂的。此外，它由Bub1和Bub3介导，而不是Mad1，Mad2和Mad3（BubR1）。我们的研究结果表明，减少紧张延迟后期发病通过一个信号，是时间和机械上不同的，从所产生的独立的动粒。
The spindle assembly checkpoint (SAC) delays anaphase onset until sister chromosomes are bound to microtubules from opposite spindle poles. Only then can dynamic microtubules produce tension across sister kinetochores. The interdependence of kinetochore attachment and tension has proved challenging to understanding SAC mechanisms. Whether the SAC responds simply to kinetochore attachment or to tension status remains obscure. Unlike higher eukaryotes, budding yeast kinetochores bind only one microtubule, simplifying the relation between attachment and tension. We developed a Taxol-sensitive yeast model to reduce tension in fully assembled spindles. Our results show that low tension on bipolar-attached kinetochores delays anaphase onset, independent of detachment. The delay is transient relative to that imposed by unattached kinetochores. Furthermore, it is mediated by Bub1 and Bub3, but not Mad1, Mad2, and Mad3 (BubR1). Our results demonstrate that reduced tension delays anaphase onset via a signal that is temporally and mechanistically distinct from that produced by unattached kinetochores.