Chromosome Segregation Laboratory, The Francis Crick Institute, London, NW1 1AT, UK; Department of Cellular Biochemistry, Kyushu University, Fukuoka, 812-8582, Japan.
Chromosome Segregation Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
Curr Opin Cell Biol. 2022 Feb;74:13-22. doi: 10.1016/j.ceb.2021.12.003. Epub 2022 Jan 8.
Loop extrusion has emerged as a prominent hypothesis for how SMC complexes shape chromosomes - single molecule in vitro observations have yielded fascinating images of this process. When not extruding loops, SMC complexes are known to topologically entrap one or more DNAs. Here, we review how structural insight into the SMC complex cohesin has led to a molecular framework for both activities: a Brownian ratchet motion, associated with topological DNA entry, might repeat itself to elicit loop extrusion. After contrasting alternative loop extrusion models, we explore whether topological loading or loop extrusion is more adept at explaining in vivo SMC complex function. SMC variants that experimentally separate topological loading from loop extrusion will in the future probe their respective contributions to chromosome biology.
环挤出已成为 SMC 复合物如何塑造染色体的一个突出假说——体外单分子观察已经产生了这个过程的迷人图像。当 SMC 复合物不挤出环时，已知它们会拓扑地困住一个或多个 DNA。在这里，我们回顾了对 SMC 复合物黏连蛋白的结构洞察力如何为这两种活性提供了一个分子框架：与拓扑 DNA 进入相关的布朗棘轮运动可能会重复自身以引发环挤出。在对比了替代的环挤出模型之后，我们探讨了拓扑加载或环挤出是否更能解释体内 SMC 复合物的功能。未来，实验上将拓扑加载与环挤出分离的 SMC 变体将探测它们各自对染色体生物学的贡献。
