Cracking the DNA Code for V(D)J Recombination
SCIE
SCOPUS
- Title
- Cracking the DNA Code for V(D)J Recombination
- Authors
- KIM, MIN SUNG; Chuenchor, Watchalee; Chen, Xuemin; Cui, Yanxiang; Zhang, Xing; Hong Zoud, Z; Gellert, Martin; Yang, Wei
- Date Issued
- 2018-04
- Publisher
- Cell Press
- 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 2.75 angstrom resolution. Both protein and DNA exhibit structural plasticity and undergo dramatic conformational changes. Coding-flank 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 60 degrees and 150 degrees in 12- and 23-RSS spacers, respectively, must occur for RAG1/2 to capture the nonamers and pair the hep-tamers 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.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/50102
- DOI
- 10.1016/j.molcel.2018.03.008
- ISSN
- 1097-2765
- Article Type
- Article
- Citation
- Molecular Cell, vol. 70, no. 2, page. 358 - 370, 2018-04
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