Cohesin forms a proteinaceous ring that is thought to link sister chromatids by entrapping DNA and counteracting the forces generated by the mitotic spindle. Whether individual cohesins encircle both sister DNAs and how cohesin opposes spindle-generated forces remains unknown. Here we perform force measurements on individual yeast cohesin complexes either bound to DNA or holding together two DNAs. By covalently closing the hinge and Smc3^Psm3–kleisin interfaces we find that the mechanical stability of the cohesin ring entrapping DNA is determined by the hinge domain. Forces of ~20 pN disengage cohesin at the hinge and release DNA, indicating that ~40 cohesin molecules are sufficient to counteract known spindle forces. Our findings provide a mechanical framework for understanding how cohesin interacts with sister chromatids and opposes the spindle-generated tension during mitosis, with implications for other force-generating chromosomal processes including transcription and DNA replication.

粘连蛋白形成一个蛋白质环，被认为通过捕获 DNA 并抵消有丝分裂纺锤体产生的力量来连接姐妹染色单体。单个黏连蛋白是否围绕着两个姐妹 DNA 以及黏连蛋白如何对抗纺锤体产生的力仍然未知。在这里，我们对与 DNA 结合或将两个 DNA 结合在一起的单个酵母黏连蛋白复合物进行力测量。通过共价闭合铰链和 Smc3^Psm3-kleisin 界面，我们发现粘连蛋白环包埋 DNA 的机械稳定性由铰链结构域决定。~20 pN 的力会使铰链处的粘连蛋白脱离并释放 DNA，表明 ~40 个粘连蛋白分子足以抵消已知的纺锤体力。我们的研究结果为理解黏连蛋白如何与姐妹染色单体相互作用并对抗有丝分裂过程中纺锤体产生的张力提供了一个机械框架，对其他产生力的染色体过程（包括转录和 DNA 复制）产生了影响。