ArticleNucleic acids research2020
Sequence-dependent dynamics of synthetic and endogenous RSSs in V(D)J recombination.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- VDJ-Insights: simplifying the annotation of genomic immunoglobulin and T cell receptor regions.Bioinformatics (Oxford, England) · 2026Article
- HTGTS-TCR-Seq for Profiling of Mouse and Human T-Cell Receptor α and β Gene Rearrangements and Diversity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Building a neural network model to define DNA sequence specificity in V(D)J recombination.Nucleic acids research · 2025Article
- Article
- Review
- The recombinase activating genes: architects of immune diversity during lymphocyte development.Frontiers in immunology · 2023Review
- An updated definition of V(D)J recombination signal sequences revealed by high-throughput recombination assays.Nucleic acids research · 2022Article
- 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
- Deciphering the regulatory genome ofeLife · 2020Article
- The Usage of Human IGHJ Genes Follows a Particular Non-random Selection: The Recombination Signal Sequence May Affect the Usage of Human IGHJ Genes.Frontiers in genetics · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Developing lymphocytes of jawed vertebrates cleave and combine distinct gene segments to assemble antigen-receptor genes. This process called V(D)J recombination that involves the RAG recombinase binding and cutting recombination signal sequences (RSSs) composed of conserved heptamer and nonamer sequences flanking less well-conserved 12- or 23-bp spacers. Little quantitative information is known about the contributions of individual RSS positions over the course of the RAG-RSS interaction. We employ a single-molecule method known as tethered particle motion to track the formation, lifetime and cleavage of individual RAG-12RSS-23RSS paired complexes (PCs) for numerous synthetic and endogenous 12RSSs. We reveal that single-bp changes, including in the 12RSS spacer, can significantly and selectively alter PC formation or the probability of RAG-mediated cleavage in the PC. We find that some rarely used endogenous gene segments can be mapped directly to poor RAG binding on their adjacent 12RSSs. Finally, we find that while abrogating RSS nicking with Ca2+ leads to substantially shorter PC lifetimes, analysis of the complete lifetime distributions of any 12RSS even on this reduced system reveals that the process of exiting the PC involves unidentified molecular details whose involvement in RAG-RSS dynamics are crucial to quantitatively capture kinetics in V(D)J recombination.
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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.