Theory and simulations of condensin mediated loop extrusion in DNA.
Theory and simulations of condensin mediated loop extrusion in DNA.
复制标题
凝聚素介导的DNA环挤压的理论与模拟。
DOI：
10.1038/s41467-021-26167-1
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发表时间：
2021-10-07
影响因子：
16.6
通讯作者：
Thirumalai D
中科院分区：
文献类型：
--
作者：
Takaki R;Dey A;Shi G;Thirumalai D
数百个兆碱基对长的人类染色体凝结在一个很小的核体积中是一种壮观的生物现象。这个过程是由染色体环的形成驱动的。 ATP 消耗马达凝缩蛋白与染色质片段相互作用，主动挤出环。受环挤压 (LE) 实时成像的启发，我们创建了一个可分析求解的模型，预测 LE 速度和步长分布作为外部负载的函数。该理论定量地符合现有的实验数据，并表明凝缩蛋白必须经历由 ATP 结合引起的大构象变化，使电机的远距离部分变得接近。使用简单模型进行的模拟证实，电机在打开和关闭状态之间转换，以便通过挤压机制挤出环，类似于细菌转录过程中 DNA 气泡形成中提出的机制。运动域方向的变化通过约 50 nm 传输，连接运动头和铰链，从而为 LE 提供变构基础。染色体是具有近十亿个碱基对的聚合物，如何包装在有限的核体积中尚不清楚。在这里，作者结合了聚合物物理学、非平衡涨落定理和模拟来定量预测凝缩蛋白的力依赖性速度和步长分布，这有助于通过环挤压来折叠染色体。
Condensation of hundreds of mega-base-pair-long human chromosomes in a small nuclear volume is a spectacular biological phenomenon. This process is driven by the formation of chromosome loops. The ATP consuming motor, condensin, interacts with chromatin segments to actively extrude loops. Motivated by real-time imaging of loop extrusion (LE), we created an analytically solvable model, predicting the LE velocity and step size distribution as a function of external load. The theory fits the available experimental data quantitatively, and suggests that condensin must undergo a large conformational change, induced by ATP binding, bringing distant parts of the motor to proximity. Simulations using a simple model confirm that the motor transitions between an open and a closed state in order to extrude loops by a scrunching mechanism, similar to that proposed in DNA bubble formation during bacterial transcription. Changes in the orientation of the motor domains are transmitted over ~50 nm, connecting the motor head and the hinge, thus providing an allosteric basis for LE. How chromosomes, which are polymers with nearly billion base pairs, are packaged in the restricted nuclear volume is not well understood. Here, the authors combine polymer physics, nonequilibrium fluctuation theorem, and simulations to quantitatively predict the force-dependent velocity and step-size distribution of condensin, which facilitates the folding of chromosomes by loop extrusion.
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DOI：
10.1126/science.aar7831
发表时间：
2018-04-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ganji M;Shaltiel IA;Bisht S;Kim E;Kalichava A;Haering CH;Dekker C
通讯作者：
Dekker C
影响因子：
7.7
作者：
Higashi TL;Pobegalov G;Tang M;Molodtsov MI;Uhlmann F
通讯作者：
Uhlmann F
DOI：
10.1073/pnas.1312393110
发表时间：
2013-10-22
影响因子：
11.1
作者：
Hinczewski, Michael;Tehver, Riina;Thirumalai, D.
通讯作者：
Thirumalai, D.
影响因子：
4.8
作者：
Chiu, A;Revenkova, E;Jessberger, R
通讯作者：
Jessberger, R
影响因子：
16.6
作者：
Alt A;Dang HQ;Wells OS;Polo LM;Smith MA;McGregor GA;Welte T;Lehmann AR;Pearl LH;Murray JM;Oliver AW
通讯作者：
Oliver AW