Drpic Danica, Pereira António J, Barisic Marin, Maresca Thomas J, Maiato Helder
Chromosome Instability & Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto, 4099-002 Porto, Portugal; Graduate Program in Areas of Basic and Applied Biology (GABBA), Instituto de Ciencias Biomedicas Abel Salazar da Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313 Porto, Portugal.
Chromosome Instability & Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto, 4099-002 Porto, Portugal.
Cell Rep. 2015 Oct 20;13(3):460-468. doi: 10.1016/j.celrep.2015.08.008. Epub 2015 Oct 8.
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.
染色体双定向发生在动粒与纺锤体微管之间最初的侧向附着转化为细胞赤道附近稳定的端对端附着之后。双定向之后，染色体受到来自纺锤体力量的张力，这在正确的动粒 - 微管附着的稳定中起关键作用。然而，在没有张力的情况下，端对端的动粒 - 微管附着最初是如何稳定的仍然是一个关键的未解决问题。为了解决这个问题，我们生成了具有未复制基因组（SMUGs）的处于有丝分裂期的果蝇S2细胞。SMUGs保留了单个浓缩染色单体，这些染色单体侧向附着于纺锤体微管。随着时间的推移，侧向附着的动粒转化为端对端附着，并经历了动粒内拉伸/结构变形，并且SMUGs在满足纺锤体组装检查点（SAC）后最终以单定向染色体退出延迟的有丝分裂。由染色体驱动蛋白产生的极向喷射力（PEFs）促进了SMUGs中从侧向到满足SAC的端对端动粒 - 微管附着的转化。因此，PEFs将侧向附着转化为稳定的端对端动粒 - 微管附着，与染色体双定向无关。
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