Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Biophys J. 2013 Jun 18;104(12):2595-606. doi: 10.1016/j.bpj.2013.05.005.
Chromosome bi-orientation at the metaphase spindle is essential for precise segregation of the genetic material. The process is error-prone, and error-correction mechanisms exist to switch misaligned chromosomes to the correct, bi-oriented configuration. Here, we analyze several possible dynamical scenarios to explore how cells might achieve correct bi-orientation in an efficient and robust manner. We first illustrate that tension-mediated feedback between the sister kinetochores can give rise to a bistable switch, which allows robust distinction between a loose attachment with low tension and a strong attachment with high tension. However, this mechanism has difficulties in explaining how bi-orientation is initiated starting from unattached kinetochores. We propose four possible mechanisms to overcome this problem (exploiting molecular noise; allowing an efficient attachment of kinetochores already in the absence of tension; a trial-and-error oscillation; and a stochastic bistable switch), and assess their impact on the bi-orientation process. Based on our results and supported by experimental data, we put forward a trial-and-error oscillation and a stochastic bistable switch as two elegant mechanisms with the potential to promote bi-orientation both efficiently and robustly.
染色体在纺锤体中期的双定向对于精确分离遗传物质至关重要。这个过程容易出错，存在错误纠正机制，可以将错位的染色体切换到正确的双定向构型。在这里，我们分析了几种可能的动力学情景，以探索细胞如何以高效和稳健的方式实现正确的双定向。我们首先说明姐妹动粒之间的张力介导反馈可以产生双稳态开关，这允许在低张力的松散附着和高张力的强附着之间进行稳健区分。然而，这种机制在解释如何从未附着的动粒开始启动双定向方面存在困难。我们提出了四种可能的机制来克服这个问题（利用分子噪声；允许在没有张力的情况下有效地附着动粒；尝试和错误的振荡；以及随机双稳态开关），并评估它们对双定向过程的影响。基于我们的结果，并得到实验数据的支持，我们提出尝试和错误的振荡和随机双稳态开关作为两种优雅的机制，有可能高效和稳健地促进双定向。
