LAUSR

Significance Condensin and cohesin are heteropentameric complexes containing two structural maintenance of chromosomes (SMC) subunits and three non-SMC subunits. SMC dimers form head and hinge domains connected by long coiled coils. Suppressor screening for head-associated non-SMC, and SMC hinge mutants of fission yeast, reveals that condensin is regulated by SUMOylation, ubiquitination, and phosphorylation, while cohesin is regulated by RNA elimination and chromatin remodeling and releasing factors. So, they are regulated by distinct pathways. However, hinge interface mutations are commonly suppressed by mutations in the kleisin N terminus. The results support a “hold and release” model, in which the head and hinge interact to form arched coiled coils that hold and release chromosomal DNAs. The head-kleisin and hinge may cooperate to regulate arched coiled coils’ orientation, which affects their interaction with DNAs. Cohesin and condensin play fundamental roles in sister chromatid cohesion and chromosome segregation, respectively. Both consist of heterodimeric structural maintenance of chromosomes (SMC) subunits, which possess a head (containing ATPase) and a hinge, 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 midmitosis, 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, and 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. Mutations in the N-terminal helix bundle [containing a helix–turn–helix (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, the head (or kleisin) and hinge may interact and collaboratively regulate the resulting coiled coils to hold and release chromosomal DNAs.