ArticleThe Journal of experimental medicine2016
RAG-mediated DNA double-strand breaks activate a cell type-specific checkpoint to inhibit pre-B cell receptor signals.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Jk Dna Gaga Motifs Are Required for Local Nucleosome Remodeling and Vk-jk Recombination.Research square · 2025Article
- 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
- Increased AID results in mutations at the CRLF2 locus implicated in Latin American ALL health disparities.Nature communications · 2024Article
- Regulation of Foxo1 expression is critical for central B cell tolerance and allelic exclusion.Cell reports · 2024Article
- MYSM1 attenuates DNA damage signals triggered by physiologic and genotoxic DNA breaks.The Journal of allergy and clinical immunology · 2024Article
- Article
- Nuclease-independent functions of RAG1 direct distinct DNA damage responses in B cells.EMBO reports · 2023Article
- The RAG1 Ubiquitin Ligase Domain Stimulates Recombination of TCRβ and TCRα Genes and Influences Development of αβ T Cell Lineages.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- 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
- Genotoxic stress signalling as a driver of macrophage diversity.Cell stress · 2022Review
- 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
- RAG enhances BCR-ABL1-positive leukemic cell growth through its endonuclease activity in vitro and in vivo.Cancer science · 2021Article
- The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination.Frontiers in genetics · 2021Review
- Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Counter Regulation of Spic by NF-κB and STAT Signaling Controls Inflammation and Iron Metabolism in Macrophages.Cell reports · 2020Article
- CLCA2 expression is associated with survival among African American women with triple negative breast cancer.PloS one · 2020Article
- Opposing Roles for the Related ETS-Family Transcription Factors Spi-B and Spi-C in Regulating B Cell Differentiation and Function.Frontiers in immunology · 2020Article
- RAG-Mediated DNA Breaks Attenuate PU.1 Activity in Early B Cells through Activation of a SPIC-BCLAF1 Complex.Cell reports · 2019Article
- Cell circuits and niches controlling B cell development.Immunological reviews · 2019Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
DNA double-strand breaks (DSBs) activate a canonical DNA damage response, including highly conserved cell cycle checkpoint pathways that prevent cells with DSBs from progressing through the cell cycle. In developing B cells, pre-B cell receptor (pre-BCR) signals initiate immunoglobulin light (Igl) chain gene assembly, leading to RAG-mediated DNA DSBs. The pre-BCR also promotes cell cycle entry, which could cause aberrant DSB repair and genome instability in pre-B cells. Here, we show that RAG DSBs inhibit pre-BCR signals through the ATM- and NF-κB2-dependent induction of SPIC, a hematopoietic-specific transcriptional repressor. SPIC inhibits expression of the SYK tyrosine kinase and BLNK adaptor, resulting in suppression of pre-BCR signaling. This regulatory circuit prevents the pre-BCR from inducing additional Igl chain gene rearrangements and driving pre-B cells with RAG DSBs into cycle. We propose that pre-B cells toggle between pre-BCR signals and a RAG DSB-dependent checkpoint to maintain genome stability while iteratively assembling Igl chain genes.
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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.