法国巴黎城市大学Karine Dubrana近期取得重要工作进展，他们研究发现，黏连蛋白复合物寡聚化可以维持断裂的DNA双链末端空间上邻近。相关研究成果U2024年10月31日在线发表于《自然—细胞生物学》杂志上。

据介绍，DNA双链断裂（DSBs）需要修复以保证基因组的稳定性。至关重要的是，DSB端必须保持在一起，以便及时维修。在酿酒酵母中，有两条途径介导DSB末端连接。一条途径利用Mre11-Rad50-Xrs2（MRX）复合物物理桥接DSB末端。另一种需要通过Exo1将DSB末端转化为单链DNA（ssDNA），但桥接蛋白尚不清楚。

研究人员发现，黏连蛋白、它的加载物和Smc5/6与Exo1一起作用，固定住DSB末端。在寡聚反应中特异性受损的粘接蛋白不能连接DSB末端，这揭示了黏连蛋白寡聚反应的功能。除了已知的姐妹染色单体内聚的重要性外，基于显微镜的微流体实验还揭示了粘接蛋白在修复中的作用，通过确保DSB末端的连接。

总之，这一研究结果表明，黏连蛋白的寡聚化可以防止DSB末端分离并促进DSB修复，揭示了一种以前未描述的作用模式和黏连蛋白在维护基因组完整性方面的作用。

附：英文原文

Title: Cohesin complex oligomerization maintains end-tethering at DNA double-strand breaks

Author: Phipps, Jamie, Toulouze, Mathias, Ducrot, Ccile, Costa, Rafal, Brocas, Clmentine, Dubrana, Karine

Issue&Volume: 2024-10-31

Abstract: 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.

DOI: 10.1038/s41556-024-01552-2

Source: https://www.nature.com/articles/s41556-024-01552-2