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In this study, Boardman et al. describe how interactions between auxiliary factor Scc2p and cohesin components Smc1p and Smc3p are crucial for the complex's ATPase activity. They propose a model in which Scc2p–Smc1p binding stimulates Smc3p's ATPase by shifting ATP into the active site, while Smc3p acetylation interferes with the Scc2p–Smc1p interface and inhibits ATPase activity.

A screen of cohesin subunit Smc3 reveals that its hinge is a nexus controlling the maintenance of sister chromatid cohesion and condensation.

A single cohesin is believed to be sufficient to tether sister chromatids. Three examples of interallelic complementation are identified and characterized in which two different mutant cohesin complexes interact to promote cohesin functions. The results support a mechanism by which multiple cohesin complexes interact on DNA to mediate cohesion and condensation.

A novel evolutionarily conserved motif termed ROCC (regulation of cohesion and condensation) is identified in the regulatory subunit of cohesin. This study offers important insights into the regulation of the maintenance of cohesion and condensation and the molecular basis for cohesin's chromatin-tethering activity.

Two aspects of cohesin's diverse functions are its regulation by acetylation and its contributions to cell viability. When Smc3p acetylation is constitutive or absent, little if any cohesion is established. Cells remain viable because Smc3p acetylation and Wpl1p regulate chromosome condensation, and a cohesin-independent segregation exists.

Comment on: The yeast SUMO isopeptidase Smt4/Ulp2 and the Polo Kinase Cdc5 act in an opposing fashion to regulate sumoylation in mitosis and cohesion at centromeres. Baldwin ML, et al. Cell Cycle 2009; 8:3406-19.

Sister chromatid cohesion is established during S phase and maintained until anaphase. The cohesin complex (Mcd1p/Scc1p, Smc1p, Smc3p Irr1p/Scc3p in budding yeast) serves a structural role as it is required at all times when cohesion exists. Pds5p co-localizes temporally and spatially with cohesin on chromosomes but is thought to serve as a regulator of cohesion maintenance during mitosis. In contrast, Ctf7p/Eco1p is required during S phase for establishment but is not required during mitosis. Here we provide genetic and biochemical evidence that the pathways of cohesion establishment and maintenance are intimately linked. Our results show that mutants in ctf7 and pds5 are synthetically lethal. Moreover, over-expression of either CTF7 or PDS5 exhibits reciprocal suppression of the other mutant’s temperature sensitivity. The suppression by CTF7 is specific for pds5 mutants as CTF7 over-expression increases the temperature sensitivity of an mcd1 mutant but has no effect on smc1 or smc3 mutants. Three additional findings provide new insights into the process of cohesion establishment. First, over-expression of ctf7 alleles deficient in acetylase activity exhibit significantly reduced suppression of the pds5 mutant but exacerbated toxicity to the mcd1 mutant. Second, using chromosome spreads and chromatin immuno-precipitation, we find neither cohesin complex nor Pds5p chromosomal localization is altered in ctf7 mutants. Finally, biochemical analysis reveals that Ctf7p and Pds5p co-immunoprecipitate, which physically links these regulators of cohesion establishment and maintenance. We propose a model whereby Ctf7p and Pds5p co-operate to facilitate efficient establishment by mediating changes in cohesin complex on chromosomes after its deposition.

Sister chromatid cohesion enables chromosomes to achieve bipolar attachment to the mitotic spindle and its dissolution is required for chromosome segregation. The cohesin complex serves as the primary molecular glue responsible for cohesion. Pds5p binds to the same chromosomal loci as the cohesin complex but plays a distinct role as a regulator of cohesion maintenance. Catenation between sister chromatids must also be removed by Topoisomerase II (Top2p) enzymatic activity to enable chromosome segregation. We identified TOP2 as a high-copy suppressor of the temperature sensitivity of pds5 mutants. TOP2 suppression is specific for pds5 mutants as it does not suppress mutants in the cohesin complex. TOP2 suppresses mini-chromosome loss in pds5 mutants indicating that it rescues a chromosome segregation defect. Surprisingly, TOP2 over-expression fails to suppress the cohesion defect of pds5 mutants, suggesting that it suppresses an additional and as yet uncharacterized defect in pds5 mutants that is essential for viability. A catalytically dead TOP2 allele suppresses pds5 temperature sensitivity, suggesting that suppression is unrelated to Top2p enzymatic function. Consistent with this idea, when the pds5 mutant is combined with the top2-4 mutant, which accumulates DNA catenanes due to defective enzymatic activity, the double mutants exhibit synthetic sickness indicating that increased catenation is toxic to pds5 cells. Our results suggest that Pds5p and Top2p cooperate to promote proper chromosome segregation by a mechanism unrelated to either cohesion or catenation/decatenation.

Pds5p is a cohesin related protein. It is required for maintenance of sister chromatid cohesion in mitosis and meiosis. Here we report that pds5-1 causes cell death in yeast Saccharomyces cerevisiae during early meiosis. The pds5-1 caused cell death possesses characteristics of apoptosis and necrosis, including externalization of phosphatidylserine at cytoplasmic membrane, accumulation of DNA breaks, chromatin condensation and fragmentation, nuclei fragmentation, membrane degeneration and cell size enlargement. Our results also suggest that (1) The defect of DNA repair; (2) The production of reactive oxygen species, in pds5-1 mutant are involved in pds5-1 induced cell death.