Lawrimore Josh, Friedman Brandon, Doshi Ayush, Bloom Kerry
Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599-3280.
Cold Spring Harb Symp Quant Biol. 2017;82:101-109. doi: 10.1101/sqb.2017.82.033696. Epub 2017 Nov 22.
ChromoShake is a three-dimensional simulator designed to explore the range of configurational states a chromosome can adopt based on thermodynamic fluctuations of the polymer chain. Here, we refine ChromoShake to generate dynamic simulations of a DNA-based motor protein such as condensin walking along the chromatin substrate. We model walking as a rotation of DNA-binding heat-repeat proteins around one another. The simulation is applied to several configurations of DNA to reveal the consequences of mechanical stepping on taut chromatin under tension versus loop extrusion on single-tethered, floppy chromatin substrates. These simulations provide testable hypotheses for condensin and other DNA-based motors functioning along interphase chromosomes. Our model reveals a novel mechanism for condensin enrichment in the pericentromeric region of mitotic chromosomes. Increased condensin dwell time at centromeres results in a high density of pericentric loops that in turn provide substrate for additional condensin.
染色体震荡模拟器（ChromoShake）是一种三维模拟器，旨在基于聚合物链的热力学涨落来探索染色体能够采取的构象状态范围。在此，我们对染色体震荡模拟器进行优化，以生成基于DNA的马达蛋白（如凝聚素沿着染色质底物移动）的动态模拟。我们将移动建模为DNA结合热重复蛋白彼此之间的旋转。该模拟应用于DNA的几种构型，以揭示在张力作用下紧绷染色质上的机械步进与单链、松弛染色质底物上的环挤压相比的后果。这些模拟为凝聚素和其他沿着间期染色体发挥作用的基于DNA的马达提供了可检验的假设。我们的模型揭示了有丝分裂染色体着丝粒周围区域凝聚素富集的一种新机制。凝聚素在着丝粒处停留时间的增加导致着丝粒周围环的高密度，进而为额外的凝聚素提供底物。
