SUMO modification regulates diverse cellular processes by targeting hundreds of proteins. However, the limited number of sumoylation enzymes raises the question of how such a large number of substrates are efficiently modified. Specifically, how genome maintenance factors are dynamically sumoylated at DNA replication and repair sites to modulate their functions is poorly understood. Here, we demonstrate a role for the conserved yeast Esc2 protein in this process by acting as a SUMO E2 cofactor. Esc2 is required for genome stability and binds to Holliday junctions and replication fork structures. Our targeted screen found that Esc2 promotes the sumoylation of a Holliday junction dissolution complex and specific replisome proteins. Esc2 does not elicit these effects via stable interactions with substrates or their common SUMO E3. Rather, we show that a SUMO-like domain of Esc2 stimulates sumoylation by exploiting a noncovalent SUMO binding site on the E2 enzyme. This role of Esc2 in sumoylation is required for Holliday junction clearance and genome stability. Our findings thus suggest that Esc2 acts as a SUMO E2 cofactor at distinct DNA structures to promote the sumoylation of specific substrates and genome maintenance.

中文翻译：

---

Esc2 通过在基因组维护中充当 SUMO E2 辅因子来协调底物特异性 sumoylation

SUMO 修饰通过靶向数百种蛋白质来调节多种细胞过程。然而，有限数量的 sumoylation 酶引发了如何有效修饰如此大量的底物的问题。具体而言，人们对基因组维持因子如何在 DNA 复制和修复位点动态地进行 sumoylated 以调节其功能知之甚少。在这里，我们通过充当 SUMO E2 辅因子来证明保守酵母 Esc2 蛋白在此过程中的作用。Esc2 是基因组稳定性所必需的，并与 Holliday 连接和复制叉结构结合。我们的目标筛选发现 Esc2 促进 Holliday 结溶解复合物和特定复制体蛋白的 sumoylation。Esc2 不会通过与底物或其常见的 SUMO E3 的稳定相互作用来引发这些影响。相当，我们显示 Esc2 的 SUMO 样结构域通过利用 E2 酶上的非共价 SUMO 结合位点来刺激 sumoylation。Esc2 在 sumoylation 中的这种作用是 Holliday 结清除和基因组稳定性所必需的。因此，我们的研究结果表明，Esc2 在不同的 DNA 结构中充当 SUMO E2 辅助因子，以促进特定底物的 sumoylation 和基因组维护。