DNA RECOMBINATION. Base triplet stepping by the Rad51/RecA family of recombinases

Science. 2015 Aug 28;349(6251):977-81. doi: 10.1126/science.aab2666.


DNA strand exchange plays a central role in genetic recombination across all kingdoms of life, but the physical basis for these reactions remains poorly defined. Using single-molecule imaging, we found that bacterial RecA and eukaryotic Rad51 and Dmc1 all stabilize strand exchange intermediates in precise three-nucleotide steps. Each step coincides with an energetic signature (0.3 kBT) that is conserved from bacteria to humans. Triplet recognition is strictly dependent on correct Watson-Crick pairing. Rad51, RecA, and Dmc1 can all step over mismatches, but only Dmc1 can stabilize mismatched triplets. This finding provides insight into why eukaryotes have evolved a meiosis-specific recombinase. We propose that canonical Watson-Crick base triplets serve as the fundamental unit of pairing interactions during DNA recombination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Pairing
  • Base Sequence
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism
  • DNA / chemistry*
  • DNA / metabolism*
  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • Evolution, Molecular
  • Homologous Recombination*
  • Humans
  • Meiosis
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Rad51 Recombinase / chemistry
  • Rad51 Recombinase / metabolism*
  • Rec A Recombinases / chemistry
  • Rec A Recombinases / metabolism*
  • Recombinases / chemistry
  • Recombinases / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Thermodynamics


  • Cell Cycle Proteins
  • DMC1 protein, S cerevisiae
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Recombinases
  • Saccharomyces cerevisiae Proteins
  • DNA
  • RAD51 protein, S cerevisiae
  • RAD51 protein, human
  • Rad51 Recombinase
  • Rec A Recombinases
  • DMC1 protein, human