Pds5 cooperates with cohesin in maintaining sister chromatid cohesion

Background: Sister chromatid cohesion depends on a complex called cohesin, which contains at least four subunits: Smc1, Smc3, Scc1 and Scc3. Cohesion is established during DNA replication, is partially dismantled in many, but not all, organisms during prophase, and is finally destroyed at the metaph ase-to-anaphase transition. A quite separate protein called Spo76 is requir ed for sister chromatid cohesion during meiosis in the ascomycete Sordaria, Spo76-like proteins are highly conserved amongst eukaryotes and a homologu e in Aspergillus nidulans, called BimD, is required for the completion of m itosis. The isolation of the cohesin subunit Smc3 as a suppressor of BimD m utations suggests that Spo76/BimD might function in the same process as coh esin. Results: We show here that the yeast homologue of Spo76, called Pds5, is es sential for establishing sister chromatid cohesion and maintaining it durin g metaphase. We also show that Pds5 co-localizes with cohesin on chromosome s, that the chromosomal association of Pds5 and cohesin is interdependent, that Scc1 recruits Pds5 to chromosomes in G1. and that its cleavage causes dissociation of Pds5 from chromosomes at the metaphase-to-anaphase transiti on. Conclusions: Our data show that Pds5 functions as part of the same process as cohesin. Sequence similarities and secondary structure predictions indic ate that Pds5 consists of tandemly repeated HEAT repeats, and might therefo re function as a protein-protein interaction scaffold, possibly in the cohe sin-DNA complex assembly.