Polar Ejection Forces Promote the Conversion from Lateral to End-on Kinetochore-Microtubule Attachments on Mono-oriented Chromosomes
Polar Ejection Forces Promote the Conversion from Lateral to End-on Kinetochore-Microtubule Attachments on Mono-oriented Chromosomes
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DOI：
10.1016/j.celrep.2015.08.008
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发表时间：
2015-10-20
期刊：
影响因子：
8.8
通讯作者：
Maiato, Helder
中科院分区：
文献类型：
--
作者：
Drpic, Danica;Pereira, Antonio J.;Maiato, Helder
在细胞赤道附近，着丝点和纺锤体微管之间最初的侧向附着转化为稳定的端接附着后，染色体发生双向定位。在双向后，染色体经历纺锤力的张力，这在正确的动粒-微管连接的稳定中起着关键作用。然而，如何在没有张力的情况下首先稳定端接的动粒-微管附着体仍然是一个关键的未回答的问题。为了解决这个问题，我们产生了进行有丝分裂的果蝇S2细胞，这些细胞带有未复制的基因组(SMUG)。Smugs保留了单个浓缩的染色单体，这些染色单体横向附着在纺锤体微管上。随着时间的推移，侧向连接的动粒转化为端接的连接，并经历着动粒内部的拉伸/结构变形，在满足纺锤体组装检查点(SAC)后，自鸣者最终退出具有单一定向染色体的延迟有丝分裂。由嗜铬激动素产生的极射出力(PEF)促进了从侧向的动粒-微管附着体的转换，从而满足了自鸣得意的SAC。因此，PEF将横向连接转化为稳定的端接着丝粒-微管连接，而与染色体双向无关。
Chromosome bi-orientation occurs after conversion of initial lateral attachments between kinetochores and spindle microtubules into stable end-on attachments near the cell equator. After bi-orientation, chromosomes experience tension from spindle forces, which plays a key role in the stabilization of correct kinetochore-microtubule attachments. However, how end-on kinetochore-microtubule attachments are first stabilized in the absence of tension remains a key unanswered question. To address this, we generated Drosophila S2 cells undergoing mitosis with unreplicated genomes (SMUGs). SMUGs retained single condensed chromatids that attached laterally to spindle microtubules. Over time, laterally attached kinetochores converted into end-on attachments and experienced intra-kinetochore stretch/structural deformation, and SMUGs eventually exited a delayed mitosis with mono-oriented chromosomes after satisfying the spindle-assembly checkpoint (SAC). Polar ejection forces (PEFs) generated by Chromokinesins promoted the conversion from lateral to end-on kinetochore-microtubule attachments that satisfied the SAC in SMUGs. Thus, PEFs convert lateral to stable end-on kinetochore-microtubule attachments, independently of chromosome bi-orientation.