Anaphase spindle mechanics prevent mis-segregation of merotelically oriented chromosomes
Anaphase spindle mechanics prevent mis-segregation of merotelically oriented chromosomes
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DOI：
10.1016/j.cub.2004.11.029
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发表时间：
2004-12-14
期刊：
影响因子：
9.2
通讯作者：
Salmon, ED
中科院分区：
文献类型：
--
作者：
Cimini, D;Cameron, LA;Salmon, ED
裂端着丝粒定向是一种着丝粒错误附着，其中单个着丝粒从两个纺锤体极而不是仅一个纺锤体极附着到微管。它可以在特定情况下有利[1-5]，不被有丝分裂检查点检测到，并在后期诱导落后染色体[6，7]。在哺乳动物细胞中，它在有丝分裂早期以高频率发生[5]，但很少有后期细胞显示落后染色体[5]。我们开发了活细胞成像方法，以确定是否以及如何有丝分裂纺锤体防止merotelic动粒产生落后的染色体。我们发现，merotelic动粒进入后期从来没有失去连接的纺锤体极，他们仍然连接到两个微管束，但这并没有阻止他们正确分离。两个微管束通常显示出不同的荧光强度，较亮的束连接到正确的极的merotelic动粒。在后期，随着纺锤体的伸长，暗束的伸长量远大于亮束。这导致了部分端部定向染色体的正确分离。我们提出了一个模型的基础上微管的比例，正确与不正确的极如何后期纺锤体动力学和微管聚合在着丝粒防止潜在的分离错误来自merotelic着丝粒取向。
Merotelic kinetochore orientation is a kinetochore misattachment in which a single kinetochore is attached to microtubules from both spindle poles instead of just one. It can be favored in specific circumstances [1-5], is not detected by the mitotic checkpoint, and induces lagging chromosomes in anaphase [6, 7]. In mammalian cells, it occurs at high frequency in early mitosis [5], but few anaphase cells show lagging chromosomes [5]. We developed live-cell imaging methods to determine whether and how the mitotic spindle prevents merotelic kinetochores from producing lagging chromosomes. We found that merotelic kinetochores entering anaphase never lost attachment to the spindle poles; they remained attached to both microtubule bundles, but this did not prevent them from segregating correctly. The two microtubule bundles usually showed different fluorescence intensities, the brighter bundle connecting the merotelic kinetochore to the correct pole. During anaphase, the dimmer bundle lengthened much more than the brighter bundle as spindle elongation occurred. This resulted in correct segregation of the merotelically oriented chromosome. We propose a model based on the ratios of microtubules to the correct versus incorrect pole for how anaphase spindle dynamics and microtubule polymerization at kinetochores prevent potential segregation errors deriving from merotelic kinetochore orientation.