PICH translocase activity is required for proper distribution of SUMOylated proteins on mitotic chromosomes

Autor: Hassebroek, Victoria, Park, Hyewon, Pandey, Nootan, Lerbakken, Brooklyn T., Aksenova, Vasilisa, Arnaoutov, Alexei, Dasso, Mary, Azuma, Yoshiaki
Jazyk: angličtina
Rok vydání: 2020
DOI: 10.1101/2020.02.06.937243
Popis: 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 ability are required for proper chromosome segregation, how these two activities function to mediate chromosome segregation remains unknown. Here, we show that PICH specifically promotes redistribution of SUMOylated proteins like SUMOylated TopoisomeraseIIα (TopoIIα) on mitotic chromosomes. Conditional depletion of PICH using the Auxin Inducible Degron (AID) system resulted in the retention of SUMOylated chromosomal proteins, including TopoIIα, indicating that PICH functions to redistribute these proteins. Replacement of endogenous PICH with exogenous PICH mutants showed that PICH translocase activity is required for SUMOylated protein redistribution. In vitro assays showed that PICH specifically regulates SUMOylated TopoIIα activity using its SUMO-binding ability. Taken together, we propose a novel function of PICH in remodeling SUMOylated chromosomal proteins to ensure faithful 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 redistribution of SUMOylated chromosomal proteins, including Topoisomerase IIα, and that function requires PICH translocase activity.
Databáze: OpenAIRE