title: A positively charged channel within the Smc1/Smc3 hinge required for sister chromatid cohesion.
abstract: Cohesin's structural maintenance of chromosome 1 (Smc1) and Smc3 are rod-shaped proteins with 50-nm long intra-molecular coiled-coil arms with a heterodimerization domain at one end and an ABC-like nucleotide-binding domain (NBD) at the other. Heterodimerization creates V-shaped molecules with a hinge at their centre. Inter-connection of NBDs by Scc1 creates a tripartite ring within which, it is proposed, sister DNAs are entrapped. To investigate whether cohesin's hinge functions as a possible DNA entry gate, we solved the crystal structure of the hinge from Mus musculus, which like its bacterial counterpart is characterized by a pseudo symmetric heterodimeric torus containing a small channel that is positively charged. Mutations in yeast Smc1 and Smc3 that together neutralize the channel's charge have little effect on dimerization or association with chromosomes, but are nevertheless lethal. Our finding that neutralization reduces acetylation of Smc3, which normally occurs during replication and is essential for cohesion, suggests that the positively charged channel is involved in a major conformational change during S phase.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurze
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Michie
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Dixon
authors.forename: Ajay
authors.initials: A
authors.lastname: Mishra
authors.forename: Takehiko
authors.initials: T
authors.lastname: Itoh
authors.forename: Syma
authors.initials: S
authors.lastname: Khalid
authors.forename: Lana
authors.initials: L
authors.lastname: Strmecki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Christian H
authors.initials: CH
authors.lastname: Haering
authors.forename: Jan
authors.initials: J
authors.lastname: Löwe
authors.forename: Kim
authors.initials: K
authors.lastname: Nasmyth
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002151:Calorimetry; D018797:Cell Cycle Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000302:isolation & purification / Q000378:metabolism*; D002842:Chromatids / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D003460:Crystallization; D019281:Dimerization; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D016133:Polymerase Chain Reaction; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1; C492317:SMC3 protein, mouse