Structure and stability of cohesin's Smc1-kleisin interaction.
A multisubunit complex called cohesin forms a huge ring structure that mediates sister chromatid cohesion, possibly by entrapping sister DNAs following replication. Cohesin's kleisin subunit Scc1 completes the ring, connecting the ABC-like ATPase heads of a V-shaped Smc1/3 heterodimer. Proteolytic cleavage of Scc1 by separase triggers sister chromatid disjunction, presumably by breaking the Scc1 bridge. One half of the SMC-kleisin bridge is revealed here by a crystal structure of Smc1's ATPase complexed with Scc1's C-terminal domain. The latter forms a winged helix that binds a pair of beta strands in Smc1's ATPase head. Mutation of conserved residues within the contact interface destroys Scc1's interaction with Smc1/3 heterodimers and eliminates cohesin function. Interaction of Scc1's N terminus with Smc3 depends on prior C terminus connection with Smc1. There is little or no turnover of Smc1-Scc1 interactions within cohesin complexes in vivo because expression of noncleavable Scc1 after DNA replication does not hinder anaphase.
Haering
Christian H
CH
Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Schoffnegger
Doris
D
Nishino
Tatsuya
T
Helmhart
Wolfgang
W
Nasmyth
Kim
K
Löwe
Jan
J
D000251:Adenosine Triphosphatases / Q000378:metabolism; D016367:Baculoviridae; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002842:Chromatids / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D019281:Dimerization; D005656:Fungal Proteins; D016193:G1 Phase; D008958:Models, Molecular; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D005656:Fungal Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1