Conformational state switching and pathways of chromosome dynamics in cell cycle
Conformational state switching and pathways of chromosome dynamics in cell cycle
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DOI：
10.1063/5.0007316
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发表时间：
2020-09-01
影响因子：
15
通讯作者：
Wang, Jin
中科院分区：
文献类型：
--
作者：
Chu, Xiakun;Wang, Jin
细胞周期是细胞的一个过程和功能，具有不同的阶段，对细胞的生长、增殖和复制至关重要。这取决于支撑基因组功能的潜在DNA分子的结构和动力学。从微观结构水平理解基因组或其功能模块染色体如何在不同时期(如间期和有丝分裂期)之间进行大规模构象转换来执行细胞周期，仍然是具有挑战性的。在这里，我们开发了一个非平衡的，激发-松弛能量格局转换模型，通过(去)凝聚来量化潜在的染色体构象转变，以实现对细胞周期的完整的微观理解。我们证明了从间期到有丝分裂相的染色体构象转变机制遵循两个阶段的情景，与实验很好地一致。相反，有丝分裂退出途径表明，存在一个过度扩张的染色体，它在末期以实验确定的中间状态重塑染色体。我们发现，从结构和动力学的角度来看，由于细胞周期的非平衡动力学，构象途径是不同的和不可逆的。我们认为，这种不可逆性主要是由于细胞周期中依赖于ATP的染色体蛋白复合体的结构维护的明显参与。我们的发现为细胞周期的微观分子结构和动力学物理机制提供了重要的见解，而不是之前更宏观的描述。我们的非平衡景观框架是通用的，适用于研究各种非平衡的物理和生物过程，如活性物质、分化/发育和癌症。
The cell cycle is a process and function of a cell with different phases essential for cell growth, proliferation, and replication. It depends on the structure and dynamics of the underlying DNA molecule, which underpins the genome function. A microscopic structural-level understanding of how a genome or its functional module chromosome performs the cell cycle in terms of large-scale conformational transformation between different phases, such as the interphase and the mitotic phase, is still challenging. Here, we develop a non-equilibrium, excitation-relaxation energy landscape-switching model to quantify the underlying chromosome conformational transitions through (de-)condensation for a complete microscopic understanding of the cell cycle. We show that the chromosome conformational transition mechanism from the interphase to the mitotic phase follows a two-stage scenario, in good agreement with the experiments. In contrast, the mitotic exit pathways show the existence of an over-expanded chromosome that recapitulates the chromosome in the experimentally identified intermediate state at the telophase. We find the conformational pathways are heterogeneous and irreversible as a result of the non-equilibrium dynamics of the cell cycle from both structural and kinetic perspectives. We suggest that the irreversibility is mainly due to the distinct participation of the ATP-dependent structural maintenance of chromosomal protein complexes during the cell cycle. Our findings provide crucial insights into the microscopic molecular structural and dynamical physical mechanism for the cell cycle beyond the previous more macroscopic descriptions. Our non-equilibrium landscape framework is general and applicable to study diverse non-equilibrium physical and biological processes such as active matter, differentiation/development, and cancer.