Molecular architecture of the HerA-NurA DNA double-strand break resection complex

FEBS Lett. 2014 Dec 20;588(24):4637-44. doi: 10.1016/j.febslet.2014.10.035. Epub 2014 Nov 11.

Abstract

DNA double-strand breaks can be repaired by homologous recombination, during which the DNA ends are long-range resected by helicase-nuclease systems to generate 3' single strand tails. In archaea, this requires the Mre11-Rad50 complex and the ATP-dependent helicase-nuclease complex HerA-NurA. We report the cryo-EM structure of Sulfolobus solfataricus HerA-NurA at 7.4Å resolution and present the pseudo-atomic model of the complex. HerA forms an ASCE hexamer that tightly interacts with a NurA dimer, with each NurA protomer binding three adjacent HerA HAS domains. Entry to NurA's nuclease active sites requires dsDNA to pass through a 23Å wide channel in the HerA hexamer. The structure suggests that HerA is a dsDNA translocase that feeds DNA into the NurA nuclease sites.

Keywords: Cryo-electron microscopy; DNA double-strand break repair; DNA resection; FtsK/HerA ATPase; Nuclease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Catalytic Domain
  • DNA / genetics
  • DNA / metabolism
  • DNA Breaks, Double-Stranded*
  • DNA Helicases / chemistry*
  • DNA Helicases / metabolism*
  • Deoxyribonucleases / chemistry*
  • Deoxyribonucleases / metabolism*
  • Models, Molecular
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Sulfolobus solfataricus / enzymology

Substances

  • Adenosine Triphosphate
  • DNA
  • Deoxyribonucleases
  • DNA Helicases