ArticleThe Journal of experimental medicine2013
The ataxia telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- ATM-dependent Phosphorylation of Nemo SQ Motifs Is Dispensable for Nemo-mediated Gene Expression Changes in Response to DNA Double-Strand Breaks.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- End resection and telomere healing of DNA double-strand breaks during nematode programmed DNA elimination.Nucleic acids research · 2024Article
- The Cyclin D3 Protein Enforces Monogenic TCRβ Expression by Mediating TCRβ Protein-Signaled Feedback Inhibition of Vβ Recombination.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Poor-Quality Vβ Recombination Signal Sequences and the DNA Damage Response ATM Kinase Collaborate to Establish TCRβ Gene Repertoire and Allelic Exclusion.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Nemo-Dependent, ATM-Mediated Signals from RAG DNA Breaks atJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Assessing DNA Damage Responses Using B Lymphocyte Cultures.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Radiofrequency EMF irradiation effects on pre-B lymphocytes undergoing somatic recombination.Scientific reports · 2021Article
- Positioning of nucleosomes containing γ-H2AX precedes active DNA demethylation and transcription initiation.Nature communications · 2021Article
- Poor quality Vβ recombination signal sequences stochastically enforce TCRβ allelic exclusion.The Journal of experimental medicine · 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
- Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis.Science translational medicine · 2019Article
- RAG-Mediated DNA Breaks Attenuate PU.1 Activity in Early B Cells through Activation of a SPIC-BCLAF1 Complex.Cell reports · 2019Article
- At the intersection of DNA damage and immune responses.Nature reviews. Immunology · 2019Review
- The Conserved ATM Kinase RAG2-S365 Phosphorylation Site Limits Cleavage Events in Individual Cells Independent of Any Repair Defect.Cell reports · 2017Article
- V(D)J Recombination Exploits DNA Damage Responses to Promote Immunity.Trends in genetics : TIG · 2017Review
- Mechanisms of central tolerance for B cells.Nature reviews. Immunology · 2017Review
- Immature Lymphocytes InhibitJournal of immunology (Baltimore, Md. : 1950) · 2017Article
- MicroRNA-3196 is inhibited by H2AX phosphorylation and attenuates lung cancer cell apoptosis by downregulating PUMA.Oncotarget · 2016Article
- Lymphocyte lineage-specific and developmental stage specific mechanisms suppress cyclin D3 expression in response to DNA double strand breaks.Cell cycle (Georgetown, Tex.) · 2016Article
- Restoration of ATM Expression in DNA-PKcs-Deficient Cells Inhibits Signal End Joining.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
Allelic exclusion is enforced through the ability of antigen receptor chains expressed from one allele to signal feedback inhibition of V-to-(D)J recombination on the other allele. To achieve allelic exclusion by such means, only one allele can initiate V-to-(D)J recombination within the time required to signal feedback inhibition. DNA double-strand breaks (DSBs) induced by the RAG endonuclease during V(D)J recombination activate the Ataxia Telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK) kinases. We demonstrate that ATM enforces Igκ allelic exclusion, and that RAG DSBs induced during Igκ recombination in primary pre-B cells signal through ATM, but not DNA-PK, to suppress initiation of additional Igκ rearrangements. ATM promotes high-density histone H2AX phosphorylation to create binding sites for MDC1, which functions with H2AX to amplify a subset of ATM-dependent signals. However, neither H2AX nor MDC1 is required for ATM to enforce Igκ allelic exclusion and suppress Igκ rearrangements. Upon activation in response to RAG Igκ cleavage, ATM signals down-regulation of Gadd45α with concomitant repression of the Gadd45α targets Rag1 and Rag2. Our data indicate that ATM kinases activated by RAG DSBs during Igκ recombination transduce transient H2AX/MDC1-independent signals that suppress initiation of further Igκ rearrangements to control Igκ allelic exclusion.
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Registered trials
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