Structural Basis and IP₆ Requirement for Pds5-Dependent Cohesin Dynamics

Highlights

• Sororin and Wapl share a previously unidentified YSR motif for Pds5 binding

• Structure of human Pds5B reveals a conserved binding site for the YSR motif

• Inositol hexakisphosphate (IP₆) is a structural cofactor of Pds5

• The IP₆-binding region of Pds5 binds to Scc1 and inhibits its binding to Smc3

Summary

The ring-shaped cohesin complex regulates transcription, DNA repair, and chromosome segregation by dynamically entrapping chromosomes to promote chromosome compaction and sister-chromatid cohesion. The cohesin ring needs to open and close to allow its loading to and release from chromosomes. Cohesin dynamics are controlled by the releasing factors Pds5 and Wapl and the cohesin stabilizer Sororin. Here, we report the crystal structure of human Pds5B bound to a conserved peptide motif found in both Wapl and Sororin. Our structure establishes the basis for how Wapl and Sororin antagonistically influence cohesin dynamics. The structure further reveals that Pds5 can bind inositol hexakisphosphate (IP₆). The IP₆-binding segment of Pds5B is shaped like the jaw of a plier lever and inhibits the binding of Scc1 to Smc3. We propose that Pds5 stabilizes a transient, open state of cohesin to promote its release from chromosomes.