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PICH regulates the abundance and localization of SUMOylated proteins on mitotic chromosomes

Hassebroek, Victoria A.
Park, Hyewon
Pandey, Nootan
Lerbakken, Brooklyn T.
Aksenova, Vasilisa
Arnaoutov, Alexei
Dasso, Mary
Azuma, Yoshiaki
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Abstract
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.
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2020-10-29
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American Society for Cell Biology
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Hassebroek, V. A., Park, H., Pandey, N., Lerbakken, B. T., Aksenova, V., Arnaoutov, A., Dasso, M., & Azuma, Y. (2020). PICH regulates the abundance and localization of SUMOylated proteins on mitotic chromosomes. Molecular biology of the cell, 31(23), 2537–2556. https://doi.org/10.1091/mbc.E20-03-0180
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