TORC1 inactivation induces a noncanonical, separase-independent cohesin degradation

Abstract

Target of rapamycin complex 1 (TORC1) integrates nutrient signals with cell growth. While its inactivation is known to trigger mitotic slippage via APC/C–Cdh1–dependent securin degradation and separase activation, the molecular basis of cohesion loss during nutrient stress has remained incompletely defined. In budding yeast, we show that TORC1 inactivation elicits a noncanonical, proteasome-dependent degradation of cohesin that is independent of securin and separase. Separase was itself destabilized upon TORC1 inactivation, yet Scc1 degradation persisted even in a separase-resistant mutant. Cohesin degradation proceeds when APC/C is impaired, indicating involvement of an atypical ubiquitin ligase. These results reveal a second, aberrant route to sister chromatid dissociation upon TORC1 inactivation, operating in parallel with the previously reported APC/C–Cdh1 pathway, via the unconventional degradation of mitotic key factors.