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bioRxiv · 10.1101/2023.05.07.539709

An intrinsically disordered kinetochore protein coordinates mechanical regulation of chromosome segregation by dynein

McGory, J. M.·Barcelos, D. M.·Verma, V.·Maresca, T. J.
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Abstract

Kinetochores connect chromosomes and spindle microtubules to maintain genomic integrity through cell division. Crosstalk between the minus-end directed motor dynein and kinetochore-microtubule attachment factors promotes accurate chromosome segregation through a poorly understood pathway. Here we identify a physical linkage between the intrinsically disordered protein Spc105 (KNL1 orthologue) and dynein using an optogenetic oligomerization assay. Core pools of the checkpoint protein BubR1 and the adaptor complex RZZ mediate the connection of Spc105 to dynein. Furthermore, a minimal segment of Spc105 that contains regions with a propensity to multimerize and binding motifs for Bub1 and BubR1 is sufficient to functionally link Spc105 to RZZ and dynein. Deletion of the minimal region from Spc105 reduces recruitment of its binding partners to bioriented kinetochores and causes chromosome mis-segregation. Restoration of normal chromosome segregation and localization of BubR1 and RZZ requires both protein binding motifs and higher-order oligomerization of Spc105. Together, our results reveal that higher-order multimerization of Spc105 is required to recruit a core pool of RZZ that modulates microtubule attachment stability to promote accurate chromosome segregation.

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McGory, J. M., Barcelos, D. M., Verma, V., Maresca, T. J.. 2023-05-09. An intrinsically disordered kinetochore protein coordinates mechanical regulation of chromosome segregation by dynein. https://doi.org/10.1101/2023.05.07.539709

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