ArticleNucleic acids research2022
An updated definition of V(D)J recombination signal sequences revealed by high-throughput recombination assays.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Unmasking human T cell receptor germline diversity: 335 novel alleles identified in 47 Pangenome reference individuals using the gAIRR Suite.Journal of advanced research · 2026Article
- A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A multi-ethnic reference map of T cell receptor germline diversity reveals evidence of natural selection on alpha chain genes.Nature communications · 2026Article
- VDJ-Insights: simplifying the annotation of genomic immunoglobulin and T cell receptor regions.Bioinformatics (Oxford, England) · 2026Article
- The nonamer code for RAG-mediated recombination in vivo.Nucleic acids research · 2025Article
- High levels of circular DNA made as immune cells develop increases the risk of leukaemia relapse.Nature · 2025Article
- Generating combinatorial diversity via engineered V(D)J-like recombination in Saccharomyces cerevisiae.Nature communications · 2025Article
- Trajectories from single-cells to PAX5-driven leukemia reveal PAX5-MYC interplay in vivo.Leukemia · 2025Article
- Building a neural network model to define DNA sequence specificity in V(D)J recombination.Nucleic acids research · 2025Article
- ALIGaToR: A tool for the automated annotation of immunoglobulin and T cell receptor genomic loci.bioRxiv : the preprint server for biology · 2025Article
- ALIGaToR: a tool for the automated annotation of immunoglobulin and T cell receptor genomic loci.Oxford open immunology · 2025Article
- Computational Analysis of T-Cell Receptor Repertoire Workflow: From T-Cell Isolation to Bioinformatics Analysis.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Enhancers within the Ig V Gene Region Orchestrate Chromatin Topology and Regulate V Gene Rearrangement Frequency to Shape the B Cell Receptor Repertoire Specificities.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Review
- DNA Repair Deficiency Regulates Immunity Response in Cancers: Molecular Mechanism and Approaches for Combining Immunotherapy.Cancers · 2023Review
- Analysis of IGH allele content in a sample group of rheumatoid arthritis patients demonstrates unrevealed population heterogeneity.Frontiers in immunology · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
In the adaptive immune system, V(D)J recombination initiates the production of a diverse antigen receptor repertoire in developing B and T cells. Recombination activating proteins, RAG1 and RAG2 (RAG1/2), catalyze V(D)J recombination by cleaving adjacent to recombination signal sequences (RSSs) that flank antigen receptor gene segments. Previous studies defined the consensus RSS as containing conserved heptamer and nonamer sequences separated by a less conserved 12 or 23 base-pair spacer sequence. However, many RSSs deviate from the consensus sequence. Here, we developed a cell-based, massively parallel assay to evaluate V(D)J recombination activity on thousands of RSSs where the 12-RSS heptamer and adjoining spacer region contained randomized sequences. While the consensus heptamer sequence (CACAGTG) was marginally preferred, V(D)J recombination was highly active on a wide range of non-consensus sequences. Select purine/pyrimidine motifs that may accommodate heptamer unwinding in the RAG1/2 active site were generally preferred. In addition, while different coding flanks and nonamer sequences affected recombination efficiency, the relative dependency on the purine/pyrimidine motifs in the RSS heptamer remained unchanged. Our results suggest RAG1/2 specificity for RSS heptamers is primarily dictated by DNA structural features dependent on purine/pyrimidine pattern, and to a lesser extent, RAG:RSS base-specific interactions.
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