Department of Biochemistry and Cell Biology, Julius Maximilian University of Würzburg, 97074 Würzburg, Germany.
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Science. 2022 Jun 3;376(6597):1087-1094. doi: 10.1126/science.abm4012. Epub 2022 Jun 2.
Structural maintenance of chromosomes (SMC) protein complexes structure genomes by extruding DNA loops, but the molecular mechanism that underlies their activity has remained unknown. We show that the active condensin complex entraps the bases of a DNA loop transiently in two separate chambers. Single-molecule imaging and cryo-electron microscopy suggest a putative power-stroke movement at the first chamber that feeds DNA into the SMC-kleisin ring upon adenosine triphosphate binding, whereas the second chamber holds on upstream of the same DNA double helix. Unlocking the strict separation of "motor" and "anchor" chambers turns condensin from a one-sided into a bidirectional DNA loop extruder. We conclude that the orientation of two topologically bound DNA segments during the SMC reaction cycle determines the directionality of DNA loop extrusion.
结构维持染色体 (SMC) 蛋白复合物通过挤出 DNA 环来构建基因组，但它们活性的分子机制仍不清楚。我们表明，活性的凝聚素复合物将 DNA 环的碱基暂时困在两个单独的腔室中。单分子成像和冷冻电子显微镜表明，在三磷酸腺苷结合时，第一个腔室可能会发生一个假设的动力冲程运动，将 DNA 送入 SMC-连接酶环，而第二个腔室则位于同一 DNA 双螺旋的上游。解开“马达”和“锚”腔室的严格分离，使凝聚素从单向 DNA 环挤出物转变为双向 DNA 环挤出物。我们的结论是，SMC 反应循环过程中两个拓扑绑定的 DNA 片段的方向决定了 DNA 环挤出的方向。
