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Structure of Mre11-Nbs1 complex yields insights into ataxia-telangiectasia-like disease mutations and DNA damage signaling.

The Mre11-Rad50-Nbs1 (MRN) complex tethers, processes and signals DNA double-strand breaks, promoting genomic stability. To understand the functional architecture of MRN, we determined the crystal structures of the Schizosaccharomyces pombe Mre11 dimeric catalytic domain alone and in complex with a fragment of Nbs1. Two Nbs1 subunits stretch around the outside of the nuclease domains of Mre11, with one subunit additionally bridging and locking the Mre11 dimer via a highly conserved asymmetrical binding motif. Our results show that Mre11 forms a flexible dimer and suggest that Nbs1 not only is a checkpoint adaptor but also functionally influences Mre11-Rad50. Clinical mutations in Mre11 are located along the Nbs1-interaction sites and weaken the Mre11-Nbs1 interaction. However, they differentially affect DNA repair and telomere maintenance in Saccharomyces cerevisiae, potentially providing insight into their different human disease pathologies.

Pubmed ID: 22705791


  • Schiller CB
  • Lammens K
  • Guerini I
  • Coordes B
  • Feldmann H
  • Schlauderer F
  • Möckel C
  • Schele A
  • Strässer K
  • Jackson SP
  • Hopfner KP


Nature structural & molecular biology

Publication Data

July 9, 2012

Associated Grants

  • Agency: Wellcome Trust, Id: 092096
  • Agency: Cancer Research UK, Id: 11224
  • Agency: European Research Council, Id: 268536
  • Agency: Cancer Research UK, Id: A11224
  • Agency: Cancer Research UK, Id: C6/A11226
  • Agency: NIAID NIH HHS, Id: U19 AI083025
  • Agency: NIAID NIH HHS, Id: U19AI83025
  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Binding Sites
  • Chromosomal Proteins, Non-Histone
  • DNA Damage
  • Dimerization
  • Humans
  • Models, Molecular
  • Mutation
  • Protein Conformation
  • Schizosaccharomyces pombe Proteins
  • Signal Transduction