PDF(Pubmed)
Abstract：
During meiosis, homologous chromosomes become associated side by side in a process known as homologous chromosome pairing. Pairing requires long range chromosome motion through a nucleus that is full of other chromosomes. It remains unclear how the cell manages to align each pair of chromosomes quickly while mitigating and resolving interlocks. Here, we use a coarse-grained molecular dynamics model to investigate how specific features of meiosis, including motor-driven telomere motion, nuclear envelope interactions, and increased nuclear size, affect the rate of pairing and the mitigation/resolution of interlocks. By creating in silico versions of three yeast strains and comparing the results of our model to experimental data, we find that a more distributed placement of pairing sites along the chromosome is necessary to replicate experimental findings. Active motion of the telomeric ends speeds up pairing only if binding sites are spread along the chromosome length. Adding a meiotic bouquet significantly speeds up pairing but does not significantly change the number of interlocks. An increase in nuclear size slows down pairing while greatly reducing the number of interlocks. Interestingly, active forces increase the number of interlocks, which raises the question: How do these interlocks resolve? Our model gives us detailed movies of interlock resolution events which we then analyze to build a step-by-step recipe for interlock resolution. In our model, interlocks must first translocate to the ends, where they are held in a quasi-stable state by a large number of paired sites on one side. To completely resolve an interlock, the telomeres of the involved chromosomes must come in close proximity so that the cooperativity of pairing coupled with random motion causes the telomeres to unwind. Together our results indicate that computational modeling of homolog pairing provides insight into the specific cell biological changes that occur during meiosis.
摘要：
在减数分裂期间,同源染色体在称为同源染色体配对的过程中并排关联。配对需要通过充满其他染色体的细胞核的长距离染色体运动。目前尚不清楚细胞如何在减轻和解决互锁的同时快速对齐每对染色体。这里,我们使用粗粒分子动力学模型来研究减数分裂的具体特征，包括马达驱动的端粒运动，核包络相互作用，增加了核大小，影响配对率和互锁的缓解/分辨率。通过创建三种酵母菌株的计算机版本，并将我们的模型结果与实验数据进行比较，我们发现，沿着染色体更多分布的配对位点是复制实验发现所必需的。只有当结合位点沿染色体长度分布时，端粒末端的主动运动才会加速配对。添加减数分裂花束可显着加速配对，但不会显着改变互锁的数量。核尺寸的增加减慢了配对,同时大大减少了互锁的数量。有趣的是,主动力增加了互锁的数量，这提出了一个问题：这些互锁是如何解决的？我们的模型为我们提供了互锁解析事件的详细电影，然后我们对其进行分析以构建互锁解析的分步配方。在我们的模型中,互锁必须首先转移到两端，在一侧，它们被大量配对位点保持在准稳定状态。要彻底解决互锁，所涉及的染色体的端粒必须非常接近，以便配对的协同性与随机运动导致端粒展开。我们的结果共同表明，同源配对的计算模型提供了对减数分裂过程中发生的特定细胞生物学变化的洞察力。
