ArticleNature2015
Orientation-specific joining of AID-initiated DNA breaks promotes antibody class switching.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 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
80 citing papers in PubMed, 118 citations in OpenAlex.
- Human antibody heavy chain variable region exon interacts with the 3' regulatory region to form a stable somatic hypermutation center.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ku70-SAP domain has an overlapping function with DNA-PKcs in limiting the lateral movement of the Ku ring along DNA.Nucleic acids research · 2026Article
- A dynamic RNA hub facilitates activation-induced cytidine deaminase recruitment to the immunoglobulin heavy-chain locus.Molecular cell · 2026Article
- CFP1 promotes B cell class switch recombination through the regulation of S region germline transcription and proliferation.iScience · 2026Article
- Chromatin-intrinsic mechanisms determine orientation-specific class switch recombination.Nature communications · 2026Article
- CFP1-mediated H3K4me3 broad domains control early B cell lineage fate determination.Nucleic acids research · 2026Article
- A dynamic RNA hub facilitates activation induced cytidine deaminase recruitment to the immunoglobulin heavy chain locus.bioRxiv : the preprint server for biology · 2026Article
- Phase separation as an emerging regulatory framework in antibody class switching and genome stability.Frontiers in immunology · 2026Review
- Explore antibody repertoire in the era of AI.Acta biochimica et biophysica Sinica · 2025Article
- Polymerase theta repairs persistent G1-induced DNA breaks in S-phase during class switch recombination.Nature communications · 2025Article
- hnRNPL-CstF64 complex: coordinating CSR and LSR in IgH locus recombination dynamics through eRNA and NHEJ regulation.Nucleic acids research · 2025Article
- Phase Separation in Chromatin Organization and Human Diseases.International journal of molecular sciences · 2025Review
- The LIM-domain-only protein LMO2 and its binding partner LDB1 are differentially required for class switch recombination.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nucleotide level mapping of uracils in murine heavy chain switch regions shows correlation between uracilation and positions of switch junctions created during class-switch recombination.NAR molecular medicine · 2025Article
- Analysis of CDR3 region diversity with different lengths in bovine immunoglobulin heavy chain genes.Frontiers in immunology · 2025Article
- Core enhancers of the 3'RR optimize IgH nuclear position and loop conformation for successful oriented class switch recombination.Nucleic acids research · 2024Article
- Orientation Regulation of Class-switch Recombination in Human B Cells.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- BRD2 promotes antibody class switch recombination by facilitating DNA repair in collaboration with NIPBL.Nucleic acids research · 2024Article
- Phosphorylation of DNA-PKcs at the S2056 cluster ensures efficient and productive lymphocyte development in XLF-deficient mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion.Nature communications · 2023Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
During B-cell development, RAG endonuclease cleaves immunoglobulin heavy chain (IgH) V, D, and J gene segments and orchestrates their fusion as deletional events that assemble a V(D)J exon in the same transcriptional orientation as adjacent Cμ constant region exons. In mice, six additional sets of constant region exons (CHs) lie 100-200 kilobases downstream in the same transcriptional orientation as V(D)J and Cμ exons. Long repetitive switch (S) regions precede Cμ and downstream CHs. In mature B cells, class switch recombination (CSR) generates different antibody classes by replacing Cμ with a downstream CH (ref. 2). Activation-induced cytidine deaminase (AID) initiates CSR by promoting deamination lesions within Sμ and a downstream acceptor S region; these lesions are converted into DNA double-strand breaks (DSBs) by general DNA repair factors. Productive CSR must occur in a deletional orientation by joining the upstream end of an Sμ DSB to the downstream end of an acceptor S-region DSB. However, the relative frequency of deletional to inversional CSR junctions has not been measured. Thus, whether orientation-specific joining is a programmed mechanistic feature of CSR as it is for V(D)J recombination and, if so, how this is achieved is unknown. To address this question, we adapt high-throughput genome-wide translocation sequencing into a highly sensitive DSB end-joining assay and apply it to endogenous AID-initiated S-region DSBs in mouse B cells. We show that CSR is programmed to occur in a productive deletional orientation and does so via an unprecedented mechanism that involves in cis Igh organizational features in combination with frequent S-region DSBs initiated by AID. We further implicate ATM-dependent DSB-response factors in enforcing this mechanism and provide an explanation of why CSR is so reliant on the 53BP1 DSB-response factor.
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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.