Responses of chromosome segregation machinery to mechanical perturbations.
Responses of chromosome segregation machinery to mechanical perturbations.
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DOI：
10.2142/biophysics.9.73
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Ishiwata S
中科院分区：
文献类型：
--
作者：
Itabashi T;Takagi J;Suzuki K;Ishiwata S
为了基因组的稳定性，需要染色体的正确分离。染色体分离的精致过程吸引了许多细胞和分子生物学家，他们关注有丝分裂细胞内部发生的情况以及每个分子如何为这一过程做出贡献，以实现准确的细胞分裂。在每次细胞分裂中将复制的基因组分配给子细胞的过程是由称为有丝分裂纺锤体的自组织结构介导的。众所周知，有丝分裂纺锤体是由微管、分子马达（驱动蛋白、细胞质动力蛋白）和其他调节分子（微管相关蛋白、激酶等）组成的多组分大分子机器。近年来，有丝分裂纺锤体的大部分蛋白质成分已被鉴定，并且这些蛋白质的功能已通过分子扰动进行了表征。因此，纺锤体组装和染色体分离的机制正在迅速揭示。然而，从力学角度来看，我们对染色体分离机制知之甚少，例如细胞内的有丝分裂纺锤体如何响应源自细胞间相互作用或环境波动的各种机械力。受控机械扰动的最新进展表明，有丝分裂纺锤体具有结构柔韧性、对所施加的外力的尺寸适应性以及强大的自组织能力。机械扰动还揭示了染色体分离机制的机械化学调节，该机制对施加的力做出反应。在这里，我们讨论有丝分裂纺锤体的结构和功能动力学的生物物理研究的当前进展。
For genome stability, the proper segregation of chromosomes is required. The exquisite process of chromosome segregation has charmed a lot of cell- and molecular biologists into watching what happens inside a mitotic cell and how each molecule contributes to this process for the accomplishment of accurate cell division. The process to partition the duplicated genome to the daughter cells in each cell division is mediated by a self-organized structure called the mitotic spindle. It is well known that the mitotic spindle is a multi-component macromolecular machine composed of microtubules, molecular motors (kinesins, cytoplasmic dynein), and other regulatory molecules (microtubule-associated proteins, kinases, etc.). In recent years, most of the protein components of the mitotic spindle have been identified and the functions of these proteins have been characterized using molecular perturbations. Thus, the mechanisms for spindle assembly and chromosome segregation are being revealed rapidly. However, the chromosome segregation machinery is poorly understood from the mechanical point of view, such as how the mitotic spindle within a cell responds to a variety of mechanical forces, originating from cell–cell interactions or environmental fluctuations. Recent advances in the controlled mechanical perturbation have indicated that the mitotic spindle possesses a structural pliability, size adaptability to the applied external forces, and a strong self-organizing ability. Mechanical perturbations revealed also the mechanochemical regulation of chromosome segregation machinery, which responds to the applied forces. Here, we discuss the current progress in the biophysical research on the architectural and functional dynamics of the mitotic spindle.