title: Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader.
abstract: The remarkable accuracy of eukaryotic cell division is partly maintained by the cohesin complex acting as a molecular glue to prevent premature sister chromatid separation. The loading of cohesin onto chromosomes is catalyzed by the Scc2-Scc4 loader complex. Here, we report the crystal structure of Scc4 bound to the N terminus of Scc2 and show that Scc4 is a tetratricopeptide repeat (TPR) superhelix. The Scc2 N terminus adopts an extended conformation and is entrapped by the core of the Scc4 superhelix. Electron microscopy (EM) analysis reveals that the Scc2-Scc4 loader complex comprises three domains: a head, body, and hook. Deletion studies unambiguously assign the Scc2N-Scc4 as the globular head domain, whereas in vitro cohesin loading assays show that the central body and the hook domains are sufficient to catalyze cohesin loading onto circular DNA, but not chromatinized DNA in vivo, suggesting a possible role for Scc4 as a chromatin adaptor.
authors.affiliation: Lincoln's Inn Fields Laboratory, The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: William C H
authors.initials: WC
authors.lastname: Chao
authors.affiliation: Lincoln's Inn Fields Laboratory, The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Murayama
authors.affiliation: Lincoln's Inn Fields Laboratory, The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Sofía
authors.initials: S
authors.lastname: Muñoz
authors.affiliation: Clare Hall Laboratory, The Francis Crick Institute, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Costa
authors.affiliation: Lincoln's Inn Fields Laboratory, The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Uhlmann
authors.affiliation: Lincoln's Inn Fields Laboratory, The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. Electronic address: martin.singleton@crick.ac.uk.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Singleton
mesh_terms: D001203:Ascomycota / Q000737:chemistry*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry*; D005656:Fungal Proteins / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D005656:Fungal Proteins