Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase.
Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase.
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DOI：
10.1083/jcb.202202085
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发表时间：
2023-08-07
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在有丝分裂期间，重复的染色体被分离到子细胞中。细胞将不正确附着的染色体与其相关的微管分离，以防止染色体分离中的错误。在这项工作中，发现通过微管的动态生长和缩短产生的机械力有效地促进了这些脱离事件。在有丝分裂过程中，姐妹染色单体通过附着在相反方向的着丝粒微管上，在着丝粒处被拉伸。这种拉伸会在分离的姐妹着丝粒上产生向内的张力。细胞利用这种张力信号来检测并纠正染色体分离中的潜在错误，通过机械张力信号通路将不正确附着的动粒从微管上分离出来。然而，导致这些脱离事件的事件顺序仍然未知。在这项研究中，我们使用微流体在多个小时内维持和观察低张力出芽酵母中期纺锤体，使我们能够阐明分离事件之前的张力历史。我们发现，在动粒磷酸化削弱低张力动粒-微管连接的条件下，需要通过微管的动态生长和缩短产生的机械力来有效促进脱离事件。我们的研究结果强调了强大的动粒微管动力学在确保有丝分裂过程中染色体分离保真度方面的关键作用。
During mitosis, duplicated chromosomes are segregated to daughter cells. The cell detaches improperly attached chromosomes from their associated microtubules to prevent errors in chromosome segregation. In this work, it is found that the mechanical forces produced via the dynamic growth and shortening of microtubules act to efficiently facilitate these detachment events. During mitosis, sister chromatids are stretched apart at their centromeres via their attachment to oppositely oriented kinetochore microtubules. This stretching generates inwardly directed tension across the separated sister centromeres. The cell leverages this tension signal to detect and then correct potential errors in chromosome segregation, via a mechanical tension signaling pathway that detaches improperly attached kinetochores from their microtubules. However, the sequence of events leading up to these detachment events remains unknown. In this study, we used microfluidics to sustain and observe low-tension budding yeast metaphase spindles over multiple hours, allowing us to elucidate the tension history prior to a detachment event. We found that, under conditions in which kinetochore phosphorylation weakens low-tension kinetochore-microtubule connections, the mechanical forces produced via the dynamic growth and shortening of microtubules is required to efficiently facilitate detachment events. Our findings underscore the critical role of robust kinetochore microtubule dynamics in ensuring the fidelity of chromosome segregation during mitosis.
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DOI：
10.1083/jcb.202007030
发表时间：
2021-06-07
期刊：
The Journal of cell biology
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作者：
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Miller RK
DOI：
10.1007/978-1-0716-1904-9_15
发表时间：
2022
期刊：
Methods in molecular biology (Clifton, N.J.)
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DOI：
10.1083/jcb.202012144
发表时间：
2021-10-04
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
Zanic M
影响因子：
64.5
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Miller MP;Asbury CL;Biggins S
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