iTHES Research Group, RIKEN, Wako, Japan.
Theoretical Biology Laboratory, RIKEN, Wako, Japan.
PLoS Comput Biol. 2018 Jun 18;14(6):e1006152. doi: 10.1371/journal.pcbi.1006152. eCollection 2018 Jun.
The mechanistic details underlying the assembly of rod-shaped chromosomes during mitosis and how they segregate from each other to act as individually mobile units remain largely unknown. Here, we construct a coarse-grained physical model of chromosomal DNA and condensins, a class of large protein complexes that plays key roles in these processes. We assume that condensins have two molecular activities: consecutive loop formation in DNA and inter-condensin attractions. Our simulation demonstrates that both of these activities and their balancing acts are essential for the efficient shaping and segregation of mitotic chromosomes. Our results also demonstrate that the shaping and segregation processes are strongly correlated, implying their mechanistic coupling during mitotic chromosome assembly. Our results highlight the functional importance of inter-condensin attractions in chromosome shaping and segregation.
在有丝分裂过程中,杆状染色体组装的机制细节以及它们如何彼此分离以作为独立的可移动单位仍然很大程度上未知。在这里,我们构建了一个染色质 DNA 和凝聚素的粗粒物理模型,凝聚素是在这些过程中起关键作用的一大类大型蛋白复合物。我们假设凝聚素有两种分子活性:在 DNA 中连续形成环和凝聚素之间的吸引力。我们的模拟表明,这两种活性及其平衡作用对于有丝分裂染色体的有效形成和分离是必不可少的。我们的结果还表明,形成和分离过程密切相关,这意味着它们在有丝分裂染色体组装过程中的机械耦联。我们的结果强调了凝聚素之间的吸引力在染色体形成和分离中的功能重要性。