Timing and checkpoints in the regulation of mitotic progression
Timing and checkpoints in the regulation of mitotic progression
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DOI：
10.1016/j.devcel.2004.06.006
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发表时间：
2004-07-01
影响因子：
11.8
通讯作者：
Sorger, PK
中科院分区：
文献类型：
--
作者：
Meraldi, P;Draviam, VM;Sorger, PK
准确的染色体分离依赖于有丝分裂进程的精确调节。调控包括控制有丝分裂的时间和连接后期开始和染色体微管附着完成的纺锤体组装检查点。在本文中，我们结合联合收割机活细胞成像的HeLa细胞和RNA干扰的蛋白质耗竭检查的功能的Mad，Bub，和动粒蛋白在有丝分裂的时间和检查点控制。我们发现，这些蛋白质中的任何一种的耗尽都可以消除由微管解聚或用RNAi阻断染色体微管附着引起的有丝分裂停滞。然而，只有当Mad 2或BubR 1而不是其他Mad和Bub蛋白失活时，有丝分裂的正常进程才会加速。此外，虽然检查点控制需要动粒，但Mad 2和BubR 1对有丝分裂时间的调节在时尚上是不依赖于动粒的。我们建议，胞质Mad 2-BubR 1是必不可少的抑制后期发病早期有丝分裂时动粒仍在组装。
Accurate chromosome segregation relies on the precise regulation of mitotic progression. Regulation involves control over the timing of mitosis and a spindle assembly checkpoint that links anaphase onset to the completion of chromosome-microtubule attachment. In this paper, we combine live-cell imaging of HeLa cells and protein depletion by RNA interference to examine the functions of the Mad, Bub, and kinetochore proteins in mitotic timing and checkpoint control. We show that the depletion of any one of these proteins abolishes the mitotic arrest provoked by depolymerizing microtubules or blocking chromosome-microtubule attachment with RNAi. However, the normal progress of mitosis is accelerated only when Mad2 or BubR1, but not other Mad and Bub proteins, are inactivated. Moreover, whereas checkpoint control requires kinetochores, the regulation of mitotic timing by Mad2 and BubR1 is kinetochore-independent in fashion. We propose that cytosolic Mad2-BubR1 is essential to restrain anaphase onset early in mitosis when kinetochores are still assembling.