论文标题
DNA中冷凝蛋白介导的环挤出的理论和模拟
Theory and Simulations of condensin mediated loop extrusion in DNA
论文作者
论文摘要
小核体积中数百种巨型基生长的人类染色体的凝结是一种壮观的现象。此过程是由染色体环的形成驱动的。食用电动机的ATP Condens与染色质片段相互作用,以主动挤出环。通过对环路挤出(LE)的实时成像和使用磁性镊子实验进行测量的动机,我们创建了一个可解析的模型,预测LE速度和步长分布是外部负载的函数。该理论定量地符合实验数据,并表明冷凝蛋白必须经历大型构象变化,这是由ATP结合引起的,将电动机的遥远部分带到接近度。使用简单模型的模拟证实,在开放状态下,电动机转变是通过经s的机制挤压回路的,类似于细菌转录过程中DNA气泡形成中提出的回路。电机域的方向的变化在$ \ sim $ 50 nm上传输,连接电动机头和铰链,从而为LE提供了变构基础。
Condensation of hundreds of mega-base-pair-long human chromosomes in a small nuclear volume is a spectacular phenomenon. This process is driven by the formation of chromosome loops. ATP consuming motor, condensin, interacts with chromatin segments to actively extrude loops. Motivated by real-time imaging of loop extrusion (LE) and measurements using magnetic tweezer experiments, we created an analytically solvable model, predicting the LE velocity and step size distribution as a function of external load. The theory fits the 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 to 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 $\sim$ 50 nm, connecting the motor head and the hinge, thus providing an allosteric basis for LE.