Sororin locks the DNA-exit gate of cohesin to preserve sister-chromatid cohesion - PubMed
14 hours ago
- #Sororin
- #cohesin
- #sister-chromatid cohesion
- Sororin's extreme C-terminal region (CTR) directly locks cohesin's DNA-exit gate by engaging the RAD21-SMC3 interface.
- Centromere-tethered Sororin-CTR restores cohesion after Sororin depletion, while constitutive chromatin tethering prevents cohesin removal, mimicking Wapl-loss phenotypes.
- Biochemical reconstitution and AlphaFold3-guided modeling reveal conserved hydrophobic and electrostatic contacts between Sororin-CTR and the RAD21-SMC3 gate, essential for cohesion.
- Mitotic phosphorylation of Sororin disrupts Pds5 binding while maintaining gate engagement, acting as a regulated switch for cohesin release.
- Sororin functions as a dual regulator, antagonizing Wapl-Pds5 and directly locking the RAD21-SMC3 exit gate to stabilize sister-chromatid cohesion.