DNA double-strand breaks (DSBs) must be repaired to ensure genome stability. Crucially, DSB-ends must be kept together for timely repair. In Saccharomyces cerevisiae, two pathways mediate DSB end-tethering. One employs the Mre11–Rad50–Xrs2 (MRX) complex to physically bridge DSB-ends. Another requires the conversion of DSB-ends into single-strand DNA (ssDNA) by Exo1, but the bridging proteins are unknown. We uncover that cohesin, its loader and Smc5/6 act with Exo1 to tether DSB-ends. Remarkably, cohesin specifically impaired in oligomerization fails to tether DSB-ends, revealing a function for cohesin oligomerization. In addition to the known importance of sister chromatid cohesion, microscopy-based microfluidic experiments unveil a role for cohesin in repair by ensuring DSB end-tethering. Altogether, our findings demonstrate that oligomerization of cohesin prevents DSB end-separation and promotes DSB repair, revealing a previously undescribed mode of action and role for cohesin in safeguarding genome integrity.

必须修复 DNA 双链断裂 （DSB） 以确保基因组稳定性。至关重要的是，DSB 端必须保持在一起以便及时修复。在酿酒酵母中，有两条途径介导 DSB 末端栓系。一种采用 Mre11-Rad50-Xrs2 （MRX） 复合物来物理桥接 DSB 末端。另一个需要 Exo1 将 DSB 末端转化为单链 DNA （ssDNA），但桥接蛋白尚不清楚。我们发现 cohesin、它的加载器和 Smc5/6 与 Exo1 一起作用以系留 DSB 末端。值得注意的是，在寡聚化中特别受损的黏连蛋白无法连接 DSB 末端，揭示了黏连蛋白寡聚化的功能。除了已知的姐妹染色单体凝聚力的重要性外，基于显微镜的微流控实验通过确保 DSB 末端栓系揭示了黏连蛋白在修复中的作用。总而言之，我们的研究结果表明，黏连蛋白的寡聚化可防止 DSB 末端分离并促进 DSB 修复，揭示了黏连蛋白在维护基因组完整性方面以前未描述的作用模式和作用。