Base triplet stepping by the Rad51/RecA family of recombinases

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Science  28 Aug 2015:
Vol. 349, Issue 6251, pp. 977-981
DOI: 10.1126/science.aab2666

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Matching DNA three bases at a time

The exchange of genetic information between DNA strands is vital for accurate DNA repair and effective meiotic cell division. Using single-molecule methods and molecular dynamics simulations, Lee et al. show that members of the family of recombinase enzymes responsible for these strand exchange reactions search for and recognize matching DNA strands three bases at a time. A single mismatch abolishes triplet recognition, except for the meiosis-specific recombinase. This enzyme can stabilize a partially mismatched triplet, reflecting the partial homology of the DNA substrates in meiosis.

Science, this issue p. 977


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.

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