ArticleCell reports2013
RAG2's acidic hinge restricts repair-pathway choice and promotes genomic stability.
Article in Cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Insights into RAG Evolution from the Identification of "Missing Link" Family A RAGL Transposons.Molecular biology and evolution · 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
- Alternative end-joining in BCR gene rearrangements and translocations.Acta biochimica et biophysica Sinica · 2022Review
- DNA Damage Response and Repair in Adaptive Immunity.Frontiers in cell and developmental biology · 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
- DNA End Joining: G0-ing to the Core.Biomolecules · 2021Review
- The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination.Frontiers in genetics · 2021Review
- Activation of DNA-PK by hairpinned DNA ends reveals a stepwise mechanism of kinase activation.Nucleic acids research · 2020Article
- Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability.Molecular cell · 2019Article
- RAG gene defects at the verge of immunodeficiency and immune dysregulation.Immunological reviews · 2019Review
- Combined Immunodeficiency With Late-Onset Progressive Hypogammaglobulinemia and Normal B Cell Count in a Patient With RAG2 Deficiency.Frontiers in pediatrics · 2019Article
- The RAG-2 Inhibitory Domain Gates Accessibility of the V(D)J Recombinase to Chromatin.Molecular and cellular biology · 2018Article
- The Conserved ATM Kinase RAG2-S365 Phosphorylation Site Limits Cleavage Events in Individual Cells Independent of Any Repair Defect.Cell reports · 2017Article
- RAG1/2 induces genomic insertions by mobilizing DNA into RAG1/2-independent breaks.The Journal of experimental medicine · 2017Article
- Riches in RAGs: Revealing the V(D)J Recombinase through High-Resolution Structures.Trends in biochemical sciences · 2017Review
- The ATM Kinase Restrains Joining of Both VDJ Signal and Coding Ends.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Restoration of ATM Expression in DNA-PKcs-Deficient Cells Inhibits Signal End Joining.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- RAG2 and XLF/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair.Nature communications · 2016Article
- Relating sequence encoded information to form and function of intrinsically disordered proteins.Current opinion in structural biology · 2015Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
V(D)J recombination-associated DNA double-strand breaks (DSBs) are normally repaired by the high-fidelity classical nonhomologous end-joining (cNHEJ) machinery. Previous studies implicated the recombination-activating gene (RAG)/DNA postcleavage complex (PCC) in regulating pathway choice by preventing access to inappropriate repair mechanisms such as homologous recombination (HR) and alternative NHEJ (aNHEJ). Here, we report that RAG2's "acidic hinge," previously of unknown function, is critical for several key steps. Mutations that reduce the hinge's negative charge destabilize the PCC, disrupt pathway choice, permit repair of RAG-mediated DSBs by the translocation-prone aNHEJ machinery, and reduce genomic stability in developing lymphocytes. Structural predictions and experimental results support our hypothesis that reduced flexibility of the hinge underlies these outcomes. Furthermore, sequence variants present in the human population reduce the hinge's negative charge, permit aNHEJ, and diminish genomic integrity.
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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.