TORC1-dependent control of fission yeast cohesin

Abstract

ABSTRACTThe Target of Rapamycin Complex 1 (TORC1) integrates cellular cues and adapts cell growth and metabolism through substrate-specific phosphorylation. A genetic screen for suppressors of a conditional mutant of the cohesin loader Mis4 identified hypomorphic mutants of TORC1. Downregulation of TORC1 enhanced the binding of cohesin and its loader to their regular sites on chromosomes. In the context of impaired cohesin loading, TORC1 downregulation rescued chromosome segregation whereas upregulation had the opposite effect, suggesting environmental cues impinge on the robustness of chromosome segregation. TORC1 co-purified with cohesin from cellular extracts and the phosphorylation level of specific residues on Mis4 and cohesin were reduced in TORC1 mutants. Cohesin mutations mimicking the non-phosphorylated state mirrored the effects of TORC1 downregulation. Challenging cells with various conditions revealed that Mis4 and TORC1 regulate a common set of genes involved in the response to environmental changes. These genes are preferentially located far from centromeres and close to telomeres. We propose that cohesin is an effector of TORC1, orchestrating alterations in chromosome structure that facilitate cellular adaptation to environmental changes.