Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage
Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage
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DOI：
10.1016/s0092-8674(00)80255-x
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发表时间：
1997-05-30
期刊：
影响因子：
64.5
通讯作者：
McKeon, F
中科院分区：
文献类型：
--
作者：
Taylor, SS;McKeon, F
有丝分裂检查点通过延迟后期直到染色体在纺锤体上对齐来确保正确的染色体分离。然而，在长时间的纺锤体损伤后，细胞最终退出有丝分裂并经历凋亡。我们在这里表明，小鼠同源的酵母有丝分裂检查点基因BUB1定位到动粒在有丝分裂。通过表达显性负突变体，我们表明，mBub1不仅是所需的检查点响应纺锤体损伤，但在正常的有丝分裂的时间行为。此外，当mBub1功能受损时，细胞逃避凋亡并继续细胞周期进程，尽管留下具有破坏的纺锤体的有丝分裂。这些数据表明，在有丝分裂的有丝分裂的有丝分裂检查点和随后的细胞凋亡事件G1的有丝分裂检查点之间的功能联系的作用，与mBub1的调节退出。
The mitotic checkpoint ensures proper chromosome segregation by delaying anaphase until chromosomes are aligned on the spindle. Following prolonged spindle damage, however, cells eventually exit mitosis and undergo apoptosis. We show here that a murine homolog of the yeast mitotic checkpoint gene BUB1 localizes to the kinetochore during mitosis. By expressing a dominant-negative mutant, we show that mBub1 is not only required for the checkpoint response to spindle damage, but acts in the timing of a normal mitosis. In addition, when mBub1 function is compromised, cells escape apoptosis and continue cell cycle progression, despite leaving mitosis with a disrupted spindle. These data demonstrate a role for kinetochore-associated mBub1 in regulating exit from mitosis, and suggest functional links between the mitotic checkpoint and subsequent apoptotic events in G1.