Loss of Kif18A Results in Spindle Assembly Checkpoint Activation at Microtubule-Attached Kinetochores
Loss of Kif18A Results in Spindle Assembly Checkpoint Activation at Microtubule-Attached Kinetochores
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DOI：
10.1016/j.cub.2018.06.026
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发表时间：
2018-09-10
期刊：
影响因子：
9.2
通讯作者：
Raaijmakers, Jonne A.
中科院分区：
文献类型：
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作者：
Janssen, Louise M. E.;Averink, Tessa V.;Raaijmakers, Jonne A.
纺锤体组装检查点（SAC）停止后期进程，直到所有着丝点获得双极性，稳定的附着于有丝分裂纺锤体。在最初的附着过程中，染色体经过振荡运动到达中期。一旦染色体被正确连接和定位，这些振荡运动被运动蛋白Kifl 8A减少，Kifl 8A的缺失导致染色体超振荡。通过使用单倍体遗传方法，我们发现Kifl 8A的缺失在野生型人类HAP1细胞中是致命的，而在sac缺陷HAP1细胞中则不是。出乎意料的是，我们发现Kifl 8A缺失后的超振荡与染色体错分离无关。相反，我们发现KiflE3A的缺失会导致SAC激活的着丝点子集的张力缺失。引人注目的是，SAC活性着丝点似乎建立了完全功能的着丝点-微管（k-Mt）附着物，允许适当的染色体分离。这些发现揭示了Kifl 8A在染色体分离中的作用，并证明SAC可以在由缺乏张力的全功能k-Mts占据的着丝点上被激活。
The spindle assembly checkpoint (SAC) halts anaphase progression until all kinetochores have obtained bipolar, stable attachments to the mitotic spindle. Upon initial attachment, chromosomes undergo oscillatory movements to reach metaphase. Once a chromosome is correctly attached and positioned, these oscillatory movements are reduced by the motor protein Kifl 8A, and loss of Kifl 8A results in chromosome hyper-oscillations. By using a haploid genetic approach, we found that loss of Kifl 8A is lethal in wild-type human HAP1 cells, but not in SAC-deficient HAP1 cells. Unexpectedly, we found that the hyper-oscillations after Kifl 8A loss are not associated with chromosome missegregations. Rather, we found that loss of KiflE3A results in a loss of tension across a subset of kinetochores accompanying SAC activation. Strikingly, the SAC active kinetochores appear to have established fully functional kinetochore-microtubule (k-Mt) attachments, allowing proper chromosome segregation. These findings shed new light on the role of Kifl 8A in chromosome segregation and demonstrate that the SAC can be activated at kinetochores that are occupied by fully functional k-Mts that lack tension.