title: DNA RECOMBINATION. Base triplet stepping by the Rad51/RecA family of recombinases.
abstract: 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.
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
authors: Ja Yil
authors: JY
authors: Lee
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. Department of Biophysics, Kyoto University, Sakyo, Kyoto, Japan.
authors: Tsuyoshi
authors: T
authors: Terakawa
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
authors: Zhi
authors: Z
authors: Qi
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
authors: Justin B
authors: JB
authors: Steinfeld
authors: Department of Chemistry, Columbia University, New York, NY, USA.
authors: Sy
authors: S
authors: Redding
authors: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA.
authors: YoungHo
authors: Y
authors: Kwon
authors: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA.
authors: William A
authors: WA
authors: Gaines
authors: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA.
authors: Weixing
authors: W
authors: Zhao
authors: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA.
authors: Patrick
authors: P
authors: Sung
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. Howard Hughes Medical Institute, Columbia University, New York, NY, USA. ecg2108@cumc.columbia.edu.
authors: Eric C
authors: EC
authors: Greene
mesh_terms: D000595:Amino Acid Sequence; D020029:Base Pairing; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D019143:Evolution, Molecular; D059765:Homologous Recombination; D006801:Humans; D008540:Meiosis; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D051135:Rad51 Recombinase / Q000737:chemistry / Q000378:metabolism*; D011938:Rec A Recombinases / Q000737:chemistry / Q000378:metabolism*; D045522:Recombinases / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D018797:Cell Cycle Proteins; C513033:DMC1 protein, S cerevisiae; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D045522:Recombinases; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; C495151:RAD51 protein, S cerevisiae; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D011938:Rec A Recombinases; C074556:DMC1 protein, human