PRJNA525996
Suppressor screening reveals common kleisin-hinge interaction in condensin and cohesin, but different modes of regulation
Cohesin and condensin play fundamental roles in sister chromatid cohesion and chromosome segregation, respectively. Both consist of heterodimeric SMC (Structural Maintenance of Chromosomes) subunits, which possess a head (containing ATPase) and a hinge, which are intervened by long coiled coils. Non-SMC subunits (Cnd1, Cnd2 and Cnd3 for condensin; Rad21, Psc3 and Mis4 for cohesin) bind to the SMC heads. Here we report a large number of spontaneous extragenic suppressors for fission yeast condensin and cohesin mutants, and their sites were determined by whole genome sequencing. Mutants of condensin's non-SMC subunits were rescued by impairing the SUMOylation pathway. Indeed, SUMOylation of Cnd2, Cnd3 and Cut3 occurs in mid-mitosis, and Cnd3 K870 SUMOylation functionally opposes Cnd subunits. In contrast, cohesin mutants rad21 and psc3 were rescued by loss of the RNA elimination pathway (Erh1, Mmi1, Red1) and loader mutant mis4 was rescued by loss of Hrp1-mediated chromatin remodeling. In addition, distinct regulations were discovered for condensin and cohesin hinge mutants too. Mutations in the N-terminal helix bundle (containing an HTH motif) of kleisin subunits (Cnd2 and Rad21), rescue virtually identical hinge interface mutations in cohesin and condensin, respectively. These mutations may regulate kleisin's interaction with the coiled coil at the SMC head, thereby revealing a common, but previously unknown suppression mechanism between the hinge and the kleisin N-domain, which is required for successful chromosome segregation. We propose that in both condensin and cohesin, head (or kleisin) and hinge may interact and collaboratively regulate the resulting coiled coils to hold and release chromosomal DNAs.