Specialized interfaces of Smc5/6 control hinge stability and DNA association

Nat Commun. 2017 Jan 30:8:14011. doi: 10.1038/ncomms14011.

Abstract

The Structural Maintenance of Chromosomes (SMC) complexes: cohesin, condensin and Smc5/6 are involved in the organization of higher-order chromosome structure-which is essential for accurate chromosome duplication and segregation. Each complex is scaffolded by a specific SMC protein dimer (heterodimer in eukaryotes) held together via their hinge domains. Here we show that the Smc5/6-hinge, like those of cohesin and condensin, also forms a toroidal structure but with distinctive subunit interfaces absent from the other SMC complexes; an unusual 'molecular latch' and a functional 'hub'. Defined mutations in these interfaces cause severe phenotypic effects with sensitivity to DNA-damaging agents in fission yeast and reduced viability in human cells. We show that the Smc5/6-hinge complex binds preferentially to ssDNA and that this interaction is affected by both 'latch' and 'hub' mutations, suggesting a key role for these unique features in controlling DNA association by the Smc5/6 complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Binding Sites
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Survival / physiology
  • Chromosomal Proteins, Non-Histone / chemistry*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cohesins
  • Crystallography, X-Ray
  • DNA Damage
  • DNA Repair / physiology*
  • DNA, Single-Stranded / metabolism*
  • DNA-Binding Proteins / chemistry
  • Humans
  • Models, Molecular
  • Multiprotein Complexes / chemistry
  • Mutagenesis, Site-Directed
  • Mutation
  • Phenotype
  • Protein Binding
  • Protein Domains / physiology
  • Protein Multimerization / physiology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Schizosaccharomyces / physiology
  • Schizosaccharomyces pombe Proteins / chemistry*
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Recombinant Proteins
  • SMC5 protein, human
  • SMC6 protein, human
  • Schizosaccharomyces pombe Proteins
  • Smc5 protein, S pombe
  • condensin complexes
  • smc6 protein, S pombe
  • Adenosine Triphosphatases