Timely anaphase onset requires a novel spindle and kinetochore complex comprising Ska1 and Ska2
Timely anaphase onset requires a novel spindle and kinetochore complex comprising Ska1 and Ska2
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DOI：
10.1038/sj.emboj.7601426
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发表时间：
2006-11-29
期刊：
影响因子：
11.4
通讯作者：
Nigg, Erich A.
中科院分区：
文献类型：
--
作者：
Hanisch, Anja;Sillje, Herman H. W.;Nigg, Erich A.
有丝分裂过程中的染色体分离要求染色体经历纺锤体微管(MTS)上的两极附着和随后纺锤体检查点的沉默。在这里，我们描述了一个新的纺锤体和动粒(KT)相关的复合体的鉴定和特征，这是及时后期开始所需的。该复合体至少由两个蛋白质组成，分别命名为BART(A)下的Ska1(S)和BART(A)下的Ska1(S)和SKA2。在前中期，Ska1与MT附着后的KTS相关。Ska1和SKA2相互作用，Ska1是SKA2体内稳定所必需的。小干扰RNA耗尽Ska1或SKA2会导致KT中这两种蛋白质的丢失。Ska蛋白的缺失不会破坏KT的整体结构，但KT纤维表现出更强的冷敏感性。最引人注目的是，Ska耗尽的细胞在类似中期的状态下经历了长时间的检查点依赖延迟。这种延迟的特征是MAD2蛋白被募集到少数KT上，并偶尔从中期平板上丢失个别染色体。这些数据表明，Ska1/2复合体在维持中期板和/或纺锤体检查点沉默中起着关键作用。
Chromosome segregation during mitosis requires chromosomes to undergo bipolar attachment on spindle microtubules (MTs) and subsequent silencing of the spindle checkpoint. Here, we describe the identification and characterisation of a novel spindle and kinetochore (KT)associated complex that is required for timely anaphase onset. The complex comprises at least two proteins, termed Ska1 ((S) under bar pindle and (K) under barT (A) under bar ssociated 1) and Ska2. Ska1 associates with KTs following MT attachment during prometaphase. Ska1 and Ska2 interact with each other and Ska1 is required for Ska2 stability in vivo. Depletion of either Ska1 or Ska2 by small interfering RNA results in the loss of both proteins from the KT. The absence of Ska proteins does not disrupt overall KT structure, but KT fibres show an increased cold-sensitivity. Most strikingly, Ska-depleted cells undergo a prolonged checkpoint-dependent delay in a metaphase-like state. This delay is characterised by the recruitment of Mad2 protein to a few KTs and the occasional loss of individual chromosomes from the metaphase plate. These data suggest that the Ska1/2 complex plays a critical role in the maintenance of the metaphase plate and/or spindle checkpoint silencing.