Pds5 Prevents the PolySUMO-Dependent Separation of Sister Chromatids

Background: The establishment, maintenance, and dissolution of sister chromatid cohesion are sequentially coordinated during the cell cycle to ensure faithful chromosome transmission. This cell-cycle-dependent regulation of cohesion is mediated, in part, by distinct posttranslational modifications of cohesin, a protein complex consisting of the Smc1-Smc3 ATPase, the Mcd1/Scc1 alpha-kleisin, and Scc3. Although cohesion is established in S phase, cohesins are not sufficient to maintain cohesion as cells progress from G2 to the metaphase-to-anaphase transition. Rather, the cohesin-associated factor Pds5 is also required to keep sisters paired until anaphase onset. How Pds5 maintains cohesion at the molecular level and whether this maintenance involves the regulation of cohesin modifications remains to be defined. Results: In pds5 mutants, we find that Mcd1 is extensively SUMOylated and that premature sister separation requires Siz2-dependent polySUMOylation. Moreover, abrogation of Pds5 function promotes the proteasome-dependent degradation of Mcd1 and a significant loss of cohesin from chromatin independently of anaphase onset. We further demonstrate that inactivation of the Slx5-Slx8 SUMO-targeted ubiquitin ligase, required for targeting polySUMOylated factors for proteasome-mediated destruction, limits Mcd1 turnover and restores both cell growth and cohesion in metaphase cells defective for Pds5 function. Conclusions: We propose that Pds5 maintains cohesion, at least in part, by antagonizing the polySUMO-dependent degradation of cohesin.