Structural and functional insights into DNA-end processing by the archaeal HerA helicase-NurA nuclease complex

Nucleic Acids Res. 2012 Apr;40(7):3183-96. doi: 10.1093/nar/gkr1157. Epub 2011 Dec 1.

Abstract

Helicase-nuclease systems dedicated to DNA end resection in preparation for homologous recombination (HR) are present in all kingdoms of life. In thermophilic archaea, the HerA helicase and NurA nuclease cooperate with the highly conserved Mre11 and Rad50 proteins during HR-dependent DNA repair. Here we show that HerA and NurA must interact in a complex with specific subunit stoichiometry to process DNA ends efficiently. We determine crystallographically that NurA folds in a toroidal dimer of intertwined RNaseH-like domains. The central channel of the NurA dimer is too narrow for double-stranded DNA but appears well suited to accommodate one or two strands of an unwound duplex. We map a critical interface of the complex to an exposed hydrophobic epitope of NurA abutting the active site. Based upon the presented evidence, we propose alternative mechanisms of DNA end processing by the HerA-NurA complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / metabolism
  • Conserved Sequence
  • Crystallography, X-Ray
  • DNA / metabolism
  • DNA Helicases / chemistry*
  • DNA Helicases / metabolism
  • Deoxyribonucleases / chemistry*
  • Deoxyribonucleases / metabolism
  • Dimerization
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Folding
  • Protein Structure, Tertiary
  • Ribonuclease H / chemistry
  • Sulfolobus solfataricus / enzymology

Substances

  • Archaeal Proteins
  • Adenosine Triphosphate
  • DNA
  • Deoxyribonucleases
  • Ribonuclease H
  • DNA Helicases

Associated data

  • PDB/2YGK