Modeling the functions of condensin in chromosome shaping and segregation.
Modeling the functions of condensin in chromosome shaping and segregation.
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DOI：
10.1371/journal.pcbi.1006152
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发表时间：
2018-06
影响因子：
4.3
通讯作者：
Tachikawa M
中科院分区：
文献类型：
--
作者：
Sakai Y;Mochizuki A;Kinoshita K;Hirano T;Tachikawa M
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充当单独的移动单元仍然很大程度上未知。在这里，我们构建了染色体 DNA 和凝缩蛋白的粗粒度物理模型，凝缩蛋白是一类在这些过程中发挥关键作用的大型蛋白质复合物。我们假设凝缩蛋白具有两种分子活性：DNA 中的连续环形成和凝缩蛋白间的吸引力。我们的模拟表明，这些活动及其平衡行为对于有丝分裂染色体的有效成形和分离至关重要。我们的结果还表明，成形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存在机械耦合。我们的结果强调了凝缩蛋白间吸引力在染色体成形和分离中的功能重要性。在细胞即将分裂之前，真核细胞中的染色体 DNA 被包装成一组离散的杆状染色体。这个过程被称为有丝分裂染色体组装或浓缩，确保遗传信息忠实地分离到子细胞中。这一复杂机制过程的核心是一类称为凝缩蛋白的蛋白质复合物。然而，凝缩蛋白如何在机械水平上支持有丝分裂染色体的组装和分离仍然难以捉摸。在这里，我们构建了染色体 DNA 纤维和凝缩蛋白分子的粗粒度物理模型，并使用计算机模拟研究凝缩蛋白如何在有丝分裂染色体组装中发挥作用。我们的结果表明，凝缩蛋白的两种活性，即染色体 DNA 纤维中连续环的形成和凝缩蛋白间的吸引力，对于有丝分裂染色体的成形和分离都是必需的，并且这些活性的平衡作用有助于协调该过程的有效进展。重要的是，我们结果中的染色体成形和分离密切相关，这意味着它们受到凝缩蛋白介导的相同潜在机制的控制。
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. Immediately before a cell divides, chromosomal DNA in a eukaryotic cell is packaged into a discrete set of rod-shaped chromosomes. This process, known as mitotic chromosome assembly or condensation, secures the faithful segregation of genetic information into daughter cells. Central to this mechanistically complex process is a class of protein complexes known as condensins. However, how condensins support the assembly and segregation of mitotic chromosomes at a mechanistic level remains elusive. Here we construct a coarse-grained physical model of chromosomal DNA fibers and condensin molecules, and study how condensins work in the mitotic chromosome assembly using computer simulations. Our results show that two activities of condensins, formation of consecutive loops in chromosomal DNA fibers and inter-condensin attractions, are necessary for both the shaping and segregation of mitotic chromosomes, and balancing acts of these activities help to coordinate the efficient progress of the processes. Importantly, chromosome shaping and segregation in our results are strongly correlated, implying that they are controlled by the same underlying mechanism mediated by condensins.
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影响因子：
64.5
作者：
Kimura, K;Hirano, T
通讯作者：
Hirano, T
影响因子：
5.8
作者：
Barysz, Helena;Kim, Ji Hun;Earnshaw, William C.
通讯作者：
Earnshaw, William C.
影响因子：
11.4
作者：
JACKSON, DA;DICKINSON, P;COOK, PR
通讯作者：
COOK, PR
影响因子：
7.5
作者：
Belmont, Andrew S.
通讯作者：
Belmont, Andrew S.
DOI：
10.1126/science.1236083
发表时间：
2013-11-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Naumova N;Imakaev M;Fudenberg G;Zhan Y;Lajoie BR;Mirny LA;Dekker J
通讯作者：
Dekker J