title: Structure of the cohesin loader Scc2.
abstract: The functions of cohesin are central to genome integrity, chromosome organization and transcription regulation through its prevention of premature sister-chromatid separation and the formation of DNA loops. The loading of cohesin onto chromatin depends on the Scc2-Scc4 complex; however, little is known about how it stimulates the cohesion-loading activity. Here we determine the large 'hook' structure of Scc2 responsible for catalysing cohesin loading. We identify key Scc2 surfaces that are crucial for cohesin loading in vivo. With the aid of previously determined structures and homology modelling, we derive a pseudo-atomic structure of the full-length Scc2-Scc4 complex. Finally, using recombinantly purified Scc2-Scc4 and cohesin, we performed crosslinking mass spectrometry and interaction assays that suggest Scc2-Scc4 uses its modular structure to make multiple contacts with cohesin.
authors.affiliation: Structural Biology of Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: William C H
authors.initials: WC
authors.lastname: Chao
authors.affiliation: Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.|Tokyo Institute of Technology, Tokyo 152-8550, Japan.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Murayama
authors.affiliation: Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Sofía
authors.initials: S
authors.lastname: Muñoz
authors.affiliation: Protein Analysis and Proteomics Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Jones
authors.affiliation: Structural Biology of Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Benjamin O
authors.initials: BO
authors.lastname: Wade
authors.affiliation: Structural Biology of Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Purkiss
authors.affiliation: Structural Biology of Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Hu
authors.affiliation: Protein Analysis and Proteomics Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Aaron
authors.initials: A
authors.lastname: Borg
authors.affiliation: Protein Analysis and Proteomics Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Ambrosius P
authors.initials: AP
authors.lastname: Snijders
authors.affiliation: Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Uhlmann
authors.affiliation: Structural Biology of Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Martin R
authors.identifier: 0000-0001-5716-7715
authors.initials: MR
authors.lastname: Singleton
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism*; D017124:Conserved Sequence; D008958:Models, Molecular; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C410592:SCC2 protein, S cerevisiae; C410593:SCC4 protein, S cerevisiae