Proper chromosome segregation is essential for faithful cell division and if not maintained results in defective cell function caused by abnormal distribution of genetic information. Polo-like kinase 1 interacting checkpoint helicase (PICH) is a DNA translocase essential for chromosome bridge resolution during mitosis. Its function in resolving chromosome bridges requires both DNA translocase activity and ability to bind chromosomal proteins modified by Small Ubiquitin-like modifier (SUMO). However, it is unclear how these activities cooperate to resolve chromosome bridges. Here, we show that PICH specifically disperses SUMO2/3 foci on mitotic chromosomes. This PICH function is apparent toward SUMOylated TopoisomeraseIIα (TopoIIα) after inhibition of TopoIIα by ICRF-193. Conditional depletion of PICH using the Auxin Inducible Degron (AID) system resulted in the retention of SUMO2/3 modified chromosomal proteins, including TopoIIα, indicating that PICH functions to reduce association of these proteins with chromosomes. Replacement of PICH with its translocase-deficient mutants led to increased SUMO2/3 foci on chromosomes suggesting that the reduction of SUMO2/3 foci requires the remodeling activity of PICH. In vitro assays showed that PICH specifically attenuates SUMOylated TopoIIα activity using its SUMO-binding ability. Taken together, we propose a novel function of PICH in remodeling SUMOylated proteins to ensure faithful chromosome segregation.

正确的染色体分离对于忠实的细胞分裂是必不可少的，如果不保持正确的染色体分离，则会因遗传信息的异常分布而导致细胞功能缺陷。Polo 样激酶 1 相互作用检查点解旋酶 (PICH) 是一种 DNA 转位酶，对于有丝分裂期间染色体桥的解析至关重要。它在解析染色体桥中的功能需要 DNA 转位酶活性和结合由小泛素样修饰剂 (SUMO) 修饰的染色体蛋白的能力。然而，尚不清楚这些活动如何合作解决染色体桥。在这里，我们表明 PICH 特异性地将 SUMO2/3 焦点分散在有丝分裂染色体上。在 ICRF-193 抑制 TopoIIα 后，这种 PICH 功能对 SUMO 化拓扑异​​构酶 IIα (TopoIIα) 很明显。使用 Auxin Inducible Degron (AID) 系统条件性耗尽 PICH 导致 SUMO2/3 修饰的染色体蛋白（包括 TopoIIα）的保留，表明 PICH 的功能是减少这些蛋白质与染色体的结合。用其转位酶缺陷型突变体替换 PICH 导致染色体上的 SUMO2/3 焦点增加，这表明 SUMO2/3 焦点的减少需要 PICH 的重塑活动。体外 试验表明，PICH 利用其 SUMO 结合能力特异性减弱 SUMO 化的 TopoIIα 活性。综上所述，我们提出了 PICH 在重塑 SUMO 化蛋白质以确保忠实的染色体分离方面的新功能。