ArticleNature structural & molecular biology2020
Cutting antiparallel DNA strands in a single active site.
Article in Nature structural & molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Nonhomologous end joining-the importance of end tethering and beyond.Genes & development · 2026Review
- RAD51 D-loop structures reveal the mechanism of eukaryotic RAD51-mediated strand exchange.Nature communications · 2025Article
- 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
- Generating combinatorial diversity via engineered V(D)J-like recombination in Saccharomyces cerevisiae.Nature communications · 2025Article
- Structural insights into human topoisomerase 3β DNA and RNA catalysis and nucleic acid gate dynamics.Nature communications · 2025Article
- TOX, through a glass, darkly.Frontiers in immunology · 2025Review
- Insights into RAG Evolution from the Identification of "Missing Link" Family A RAGL Transposons.Molecular biology and evolution · 2023Article
- RAG genomic variation causes autoimmune diseases through specific structure-based mechanisms of enzyme dysregulation.iScience · 2023Article
- Review
- Dynamics of the Artemis and DNA-PKcs Complex in the Repair of Double-Strand Breaks.Journal of molecular biology · 2022Review
- An updated definition of V(D)J recombination signal sequences revealed by high-throughput recombination assays.Nucleic acids research · 2022Article
- Structural and biochemical basis for DNA and RNA catalysis by human Topoisomerase 3β.Nature communications · 2022Article
- Structural insights into the evolution of the RAG recombinase.Nature reviews. Immunology · 2022Review
- Inner workings of RAG recombinase and its specialization for adaptive immunity.Current opinion in structural biology · 2021Review
- 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
- Dimers of DNA-PK create a stage for DNA double-strand break repair.Nature structural & molecular biology · 2021Article
- Mechanism and regulation of P element transposition.Open biology · 2020Review
- Temporally uncoupled signal and coding joint formation in human V(D)J recombination.Molecular immunology · 2020Article
- The molecular basis and disease relevance of non-homologous DNA end joining.Nature reviews. Molecular cell biology · 2020Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
A single enzyme active site that catalyzes multiple reactions is a well-established biochemical theme, but how one nuclease site cleaves both DNA strands of a double helix has not been well understood. In analyzing site-specific DNA cleavage by the mammalian RAG1-RAG2 recombinase, which initiates V(D)J recombination, we find that the active site is reconfigured for the two consecutive reactions and the DNA double helix adopts drastically different structures. For initial nicking of the DNA, a locally unwound and unpaired DNA duplex forms a zipper via alternating interstrand base stacking, rather than melting as generally thought. The second strand cleavage and formation of a hairpin-DNA product requires a global scissor-like movement of protein and DNA, delivering the scissile phosphate into the rearranged active site.
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Registered trials
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.