Kinetochore chemistry is sensitive to tension and may link mitotic forces to a cell cycle checkpoint.

Kinetochore chemistry is sensitive to tension and may link mitotic forces to a cell cycle checkpoint.
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着丝粒化学对张力敏感,可能将有丝分裂力与细胞周期检查点联系起来。

DOI:
10.1083/jcb.130.4.929
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发表时间:
1995-08
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Gorbsky GJ
Gorbsky GJ
中科院分区:
其他
文献类型:
--
作者:
Nicklas RB;Ward SC;Gorbsky GJ

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一些细胞具有质量控制检查点,可以检测单个错误附着的染色体并延迟后期的开始,从而为错误纠正留出时间。附着过程中的机械错误一定与细胞周期进程的化学调节有关。3F 3抗体检测可能作为所需连接的磷酸化动粒蛋白(Gorbsky,G. J.,和W. A.里基茨。1993. 122:1311-1321)。我们通过直接显微操作实验表明,张力改变了动粒蛋白的磷酸化。张力,无论是从显微操作针或从正常的有丝分裂力,导致3F 3所识别的动粒蛋白的去磷酸化。如果张力是不存在的,无论是自然的还是由于染色体分离的显微操作,蛋白质磷酸化。同样直接的实验将张力确定为检查点信号:来自错接染色体上的微针的张力导致分裂后期(Li,X.,和R. B。尼可拉斯1995.自然(伦敦)。373:630-632),并且我们在此表明,由于染色体从纺锤体分离而导致的张力的缺乏无限期地延迟了后期。因此,张力的缺乏与动粒磷酸化和延迟的后期开始有关。我们认为,张力引起的动粒蛋白脱磷酸化是检查点的全部清除信号。证据是间接的,但丰富。无论如何,张力改变了动粒化学。张力很可能直接影响化学反应,通过改变张力敏感蛋白的构象,直接导致去磷酸化。
Some cells have a quality control checkpoint that can detect a single misattached chromosome and delay the onset of anaphase, thus allowing time for error correction. The mechanical error in attachment must somehow be linked to the chemical regulation of cell cycle progression. The 3F3 antibody detects phosphorylated kinetochore proteins that might serve as the required link (Gorbsky, G. J., and W. A. Ricketts. 1993. J. Cell Biol. 122:1311-1321). We show by direct micromanipulation experiments that tension alters the phosphorylation of kinetochore proteins. Tension, whether from a micromanipulation needle or from normal mitotic forces, causes dephosphorylation of the kinetochore proteins recognized by 3F3. If tension is absent, either naturally or as a result of chromosome detachment by micromanipulation, the proteins are phosphorylated. Equally direct experiments identify tension as the checkpoint signal: tension from a microneedle on a misattached chromosome leads to anaphase (Li, X., and R. B. Nicklas. 1995. Nature (Lond.). 373:630-632), and we show here that the absence of tension caused by detaching chromosomes from the spindle delays anaphase indefinitely. Thus, the absence of tension is linked to both kinetochore phosphorylation and delayed anaphase onset. We propose that the kinetochore protein dephosphorylation caused by tension is the all clear signal to the checkpoint. The evidence is circumstantial but rich. In any event, tension alters kinetochore chemistry. Very likely, tension affects chemistry directly, by altering the conformation of a tension-sensitive protein, which leads directly to dephosphorylation.