PICH regulates the abundance and localization of SUMOylated proteins on mitotic chromosomes.
PICH regulates the abundance and localization of SUMOylated proteins on mitotic chromosomes.
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DOI：
10.1091/mbc.e20-03-0180
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发表时间：
2020-11-01
影响因子：
3.3
通讯作者：
Azuma Y
中科院分区：
文献类型：
--
作者：
Hassebroek VA;Park H;Pandey N;Lerbakken BT;Aksenova V;Arnaoutov A;Dasso M;Azuma Y
正确的染色体分离对于忠实的细胞分裂至关重要，如果不保持这种分离，就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，对于有丝分裂过程中染色体桥的解析至关重要。它在解决染色体桥方面的功能需要 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来解决染色体桥问题。在这里，我们证明 PICH 特异性地将 SUMO2/3 焦点分散在有丝分裂染色体上。 ICRF-193 抑制 TopoIIα 后，这种 PICH 功能对 SUMO 化拓扑异构酶 IIα (TopoIIα) 很明显。使用生长素诱导降解决定子 (AID) 系统条件性去除 PICH 导致 SUMO2/3 修饰的染色体蛋白（包括 TopoIIα）保留，表明 PICH 的功能是减少这些蛋白与染色体的关联。用其易位酶缺陷突变体替换PICH导致染色体上SUMO2/3焦点增加，表明SUMO2/3焦点的减少需要PICH的重塑活性。体外测定表明，PICH 利用其 SUMO 结合能力特异性减弱 SUMO 化的 TopoIIα 活性。综合这些结果，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。
Proper chromosome segregation is essential for faithful cell division and if not maintained results in defective cell function caused by the 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 the 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 topoisomerase IIα (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 the 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. Taking the results together, we propose a novel function of PICH in remodeling SUMOylated proteins to ensure faithful chromosome segregation.