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PICH promotes SUMOylated TopoisomeraseIIα dissociation from mitotic centromeres for proper chromosome segregation

Polo-like kinase interacting checkpoint helicase (PICH) is a SNF2 family DNA translocase and is a Small Ubiquitin-like modifier (SUMO) binding protein. Despite that both translocase activity and SUMO-binding activity are required for proper chromosome segregation, how these two activities function to mediate chromosome segregation remains unknown. Here, we show that PICH specifically promotes dissociation of SUMOylated TopoisomeraseIIα (TopoIIα) from mitotic chromosomes. When TopoIIα is stalled by treatment of cells with a potent TopoII inhibitor, ICRF-193, TopoIIα becomes SUMOylated, and this promotes its interaction with PICH. Conditional depletion of PICH using the Auxin Inducible Degron (AID) system resulted in retention of SUMOylated TopoIIα on chromosomes, indicating that PICH removes stalled SUMOylated TopoIIα from chromosomes. In vitro assays showed that PICH specifically regulates SUMOylated TopoIIα activity using its SUMO-binding and translocase activities. Taken together, we propose a novel mechanism for how PICH acts on stalled SUMOylated TopoIIα for proper chromosome segregation. Summary Statement Polo-like kinase interacting checkpoint helicase (PICH) interacts with SUMOylated proteins to mediate proper chromosome segregation during mitosis. The results demonstrate that PICH promotes dissociation of SUMOylated TopoisomeraseIIα from chromosomes and that function leads to proper chromosome segregation.