Structure and stability of cohesin's Smc1-kleisin interaction

Mol Cell. 2004 Sep 24;15(6):951-64. doi: 10.1016/j.molcel.2004.08.030.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Baculoviridae
  • Binding Sites
  • Cell Cycle Proteins / metabolism*
  • Chromatids / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Crystallography, X-Ray
  • DNA Mutational Analysis
  • Dimerization
  • Fungal Proteins
  • G1 Phase
  • Models, Molecular
  • Mutation
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Fungal Proteins
  • Nuclear Proteins
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • cohesins
  • structural maintenance of chromosome protein 1
  • Adenosine Triphosphatases

Associated data

  • PDB/1W1W