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Cracking the DNA Code for V(D)J Recombination.

  • 저널명MOLECULAR CELL, 70(2):358-370.e4. doi: 10.1016/j.molcel.2018.03.008
    • 담당교수Min-Sung Kim
    • 조회65
    • 작성자최고관리자
    • 2020-03-02


    ■ Abstract

    To initiate V(D)J recombination for generating the adaptive immune response of vertebrates, RAG1/2 recombinase cleaves DNA at a pair of recombination signal sequences, the 12- and 23-RSS. We have determined crystal and cryo-EM structures of RAG1/2 with DNA in the pre-reaction and hairpinforming complexes up to 2.75A° resolution. Both protein and DNA exhibit structural plasticity and undergo dramatic conformational changes. Codingflank DNAs extensively rotate, shift, and deform for nicking and hairpin formation. Two intertwined RAG1 subunits crisscross four times between the asymmetric pair of severely bent 12/23-RSS DNAs. Location-sensitive bending of 60and 150in 12- and 23-RSS spacers, respectively, must occur for RAG1/2 to capture the nonamers and pair the heptamers for symmetric double-strand breakage. DNA pairing is thus sequence-context dependent and structure specific, which partly explains the ‘‘beyond 12/23’’ restriction. Finally, catalysis in crystallo reveals the process of DNA hairpin formation and its stabilization by interleaved base stacking.