Authors
Mishra, A., Butler, R. J., Koch, L. B., Spanos, C., Severson, A. F., Marston, A. L., Boerner, G. V.
Abstract
Accurate chromosome segregation requires the spatiotemporally regulated removal of sister chromatid cohesion. Cohesin cleavage by the endopeptidase separase depends on destruction of its inhibitor securin by the ubiquitin-proteasome system (UPS) and on phosphorylation-mediated priming of the cohesin kleisin subunit. Whether the UPS also contributes to cohesin priming has remained unknown. Here, we show that the 26S proteasome mediates cohesin removal during meiosis II through branches of two parallel pathways. Using separation-of-function mutants targeting either the proteasome's core or regulatory particles, we identify a proteasome function that is required specifically for centromeric cohesin removal during meiosis II but dispensable for separase activation. Defects in this proteasome function causes centromeric accumulation of phosphatase anchor shugoshin (Sgo1), impaired cleavage of meiotic kleisin Rec8, and frequent failure of sister chromatid segregation. Bypassing the requirement for Rec8 priming, either through a phosphomimetic rec8 allele or by separase-independent Rec8 cleavage, restores chromosome segregation, demonstrating that the proteasome mediates cohesin removal independently of its established role in activating separase. Consistent with a direct role, proteasomes localize prominently to kinetochores during meiosis II. Together, these findings identify the proteasome as a dual-function regulator that mediates both separase activation and cohesin priming, revealing how a single proteolytic machine coordinates the two molecular pathways underlying stepwise chromosome segregation during meiosis.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 24 Aug 2026.
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