IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy.
IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy; Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (IGM-CNR), Via Abbiategrasso 207, 27100 Pavia, Italy.
Cell Rep. 2021 Aug 3;36(5):109485. doi: 10.1016/j.celrep.2021.109485.
Structural maintenance of chromosomes (SMCs) complexes, cohesin, condensin, and Smc5/6, are essential for viability and participate in multiple processes, including sister chromatid cohesion, chromosome condensation, and DNA repair. Here we show that SUMO chains target all three SMC complexes and are antagonized by the SUMO protease Ulp2 to prevent their turnover. We uncover that the essential role of the cohesin-associated subunit Pds5 is to counteract SUMO chains jointly with Ulp2. Importantly, fusion of Ulp2 to kleisin Scc1 supports viability of PDS5 null cells and protects cohesin from proteasomal degradation mediated by the SUMO-targeted ubiquitin ligase Slx5/Slx8. The lethality of PDS5-deleted cells can also be bypassed by simultaneous loss of the proliferating cell nuclear antigen (PCNA) unloader, Elg1, and the cohesin releaser, Wpl1, but only when Ulp2 is functional. Condensin and Smc5/6 complex are similarly guarded by Ulp2 against unscheduled SUMO chain assembly, which we propose to time the availability of SMC complexes on chromatin.
染色体结构维持(SMC)复合物、黏合蛋白、凝聚蛋白和 Smc5/6 对于生存是必需的,并参与多个过程,包括姐妹染色单体黏合、染色体凝聚和 DNA 修复。在这里,我们表明 SUMO 链靶向所有三种 SMC 复合物,并被 SUMO 蛋白酶 Ulp2 拮抗以防止其周转。我们发现黏合蛋白相关亚基 Pds5 的必需作用是与 Ulp2 一起拮抗 SUMO 链。重要的是,Ulp2 与 kleisin Scc1 的融合支持 PDS5 缺失细胞的存活,并保护黏合蛋白免受由 SUMO 靶向泛素连接酶 Slx5/Slx8 介导的蛋白酶体降解。只有当 Ulp2 起作用时,同时缺失增殖细胞核抗原(PCNA)卸载物 Elg1 和黏合蛋白释放因子 Wpl1 也可以绕过 PDS5 缺失细胞的致死性。凝聚蛋白和 Smc5/6 复合物也同样受到 Ulp2 的保护,防止非计划的 SUMO 链组装,我们提出这可以控制 SMC 复合物在染色质上的可用性。