ArticleNature structural & molecular biology2018
DNA melting initiates the RAG catalytic pathway.
Article in Nature structural & molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed.
- 53BP1 orchestrates sequence feature of RAG targets to balance DNA repair outcomes during V(D)J recombination.Science advances · 2026Article
- How RAG1/2 evolved from ancestral transposases to initiate V(D)J recombination without transposition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Building a neural network model to define DNA sequence specificity in V(D)J recombination.Nucleic acids research · 2025Article
- Probing mechanical selection in diverse eukaryotic genomes through accurate prediction of 3D DNA mechanics.bioRxiv : the preprint server for biology · 2024Article
- Review
- Locus architecture and RAG scanning determine antibody diversity.Trends in immunology · 2023Review
- An updated definition of V(D)J recombination signal sequences revealed by high-throughput recombination assays.Nucleic acids research · 2022Article
- The role of chromatin loop extrusion in antibody diversification.Nature reviews. Immunology · 2022Review
- Structural insights into the evolution of the RAG recombinase.Nature reviews. Immunology · 2022Review
- DNA Damage Response and Repair in Adaptive Immunity.Frontiers in cell and developmental biology · 2022Review
- Inner workings of RAG recombinase and its specialization for adaptive immunity.Current opinion in structural biology · 2021Review
- Genome-Wide Identification, Characterization, and Expression Analysis of DDE_Tnp_4 Family Genes inAntibiotics (Basel, Switzerland) · 2021Article
- RAG2 abolishes RAG1 aggregation to facilitate V(D)J recombination.Cell reports · 2021Article
- Clinical Manifestations, Mutational Analysis, and Immunological Phenotype in Patients with RAG1/2 Mutations: First Cases Series from Mexico and Description of Two Novel Mutations.Journal of clinical immunology · 2021Article
- Structures of ISCth4 transpososomes reveal the role of asymmetry in copy-out/paste-in DNA transposition.The EMBO journal · 2021Article
- Mechanism and regulation of P element transposition.Open biology · 2020Review
- Structural basis for the activation and suppression of transposition during evolution of the RAG recombinase.The EMBO journal · 2020Article
- The recent advances in non-homologous end-joining through the lens of lymphocyte development.DNA repair · 2020Review
- Sequence-dependent dynamics of synthetic and endogenous RSSs in V(D)J recombination.Nucleic acids research · 2020Article
- Cutting antiparallel DNA strands in a single active site.Nature structural & molecular biology · 2020Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The mechanism for initiating DNA cleavage by DDE-family enzymes, including the RAG endonuclease, which initiates V(D)J recombination, is not well understood. Here we report six cryo-EM structures of zebrafish RAG in complex with one or two intact recombination signal sequences (RSSs), at up to 3.9-Å resolution. Unexpectedly, these structures reveal DNA melting at the heptamer of the RSSs, thus resulting in a corkscrew-like rotation of coding-flank DNA and the positioning of the scissile phosphate in the active site. Substrate binding is associated with dimer opening and a piston-like movement in RAG1, first outward to accommodate unmelted DNA and then inward to wedge melted DNA. These precleavage complexes show limited base-specific contacts of RAG at the conserved terminal CAC/GTG sequence of the heptamer, thus suggesting conservation based on a propensity to unwind. CA and TG overwhelmingly dominate terminal sequences in transposons and retrotransposons, thereby implicating a universal mechanism for DNA melting during the initiation of retroviral integration and DNA transposition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.