ArticleProceedings of the National Academy of Sciences of the United States of America2010
Autoinhibition of DNA cleavage mediated by RAG1 and RAG2 is overcome by an epigenetic signal in V(D)J recombination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- 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
- Design and characterization of hyperactive mutants of the Agrobacterium tumefaciens telomere resolvase, TelA.PloS one · 2024Article
- Nuclease-independent functions of RAG1 direct distinct DNA damage responses in B cells.EMBO reports · 2023Article
- The recombinase activating genes: architects of immune diversity during lymphocyte development.Frontiers in immunology · 2023Review
- Structural insights into the evolution of the RAG recombinase.Nature reviews. Immunology · 2022Review
- V(D)J Recombination: Recent Insights in Formation of the Recombinase Complex and Recruitment of DNA Repair Machinery.Frontiers in cell and developmental biology · 2022Review
- The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination.The Journal of experimental medicine · 2021Article
- Binding and allosteric transmission of histone H3 Lys-4 trimethylation to the recombinase RAG-1 are separable functions of the RAG-2 plant homeodomain finger.The Journal of biological chemistry · 2020Article
- Alterations in chromatin at antigen receptor loci define lineage progression during B lymphopoiesis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Nucleolar localization of RAG1 modulates V(D)J recombination activity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Cutting antiparallel DNA strands in a single active site.Nature structural & molecular biology · 2020Article
- The ESC: The Dangerous By-Product of V(D)J Recombination.Frontiers in immunology · 2019Review
- RAG2 localization and dynamics in the pre-B cell nucleus.PloS one · 2019Article
- The RAG-2 Inhibitory Domain Gates Accessibility of the V(D)J Recombinase to Chromatin.Molecular and cellular biology · 2018Article
- Cracking the DNA Code for V(D)J Recombination.Molecular cell · 2018Article
- New insights into the evolutionary origins of the recombination-activating gene proteins and V(D)J recombination.The FEBS journal · 2017Review
- H3K4me3 induces allosteric conformational changes in the DNA-binding and catalytic regions of the V(D)J recombinase.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Riches in RAGs: Revealing the V(D)J Recombinase through High-Resolution Structures.Trends in biochemical sciences · 2017Review
- RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2.Nucleic acids research · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Gene assembly of the variable domain of antigen receptors is initiated by DNA cleavage by the RAG1-RAG2 protein complex at sites flanking V, D, and J gene segments. Double-strand breaks are produced via a single-strand nick that is converted to a hairpin end on coding DNA and a blunt end on the neighboring recombination signal sequence. We demonstrate that the C-terminal regions of purified murine RAG1 (aa 1009-1040) and RAG2 (aa 388-520, including a plant homeodomain [PHD domain]) collaborate to inhibit the hairpinning stage of DNA cleavage. The C-terminal region of RAG2 stabilizes the RAG1/2 heterotetramer but destabilizes the RAG-DNA precleavage complex. This destabilization is reversed by binding of the PHD domain to a histone H3 peptide trimethylated on lysine 4 (H3K4me3). The addition of H3K4me3 likewise alleviates the RAG1/RAG2 C-terminus-mediated inhibition of hairpinning and the PHD-mediated inhibition of transposition activity. Thus a negative regulatory function of the noncore regions of RAG1/2 limits the RAG endonuclease activity in the absence of an activating methylated histone tail bound to the complex.
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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.