ArticleProceedings of the National Academy of Sciences of the United States of America2015
Single-molecule analysis of RAG-mediated V(D)J DNA cleavage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed.
- The nonamer code for RAG-mediated recombination in vivo.Nucleic acids research · 2025Article
- Building a neural network model to define DNA sequence specificity in V(D)J recombination.Nucleic acids research · 2025Article
- Review
- Deciphering the regulatory genome ofeLife · 2020Article
- Poor quality Vβ recombination signal sequences stochastically enforce TCRβ allelic exclusion.The Journal of experimental medicine · 2020Article
- Sequence-dependent dynamics of synthetic and endogenous RSSs in V(D)J recombination.Nucleic acids research · 2020Article
- Targeting Chromosomal Architectural HMGB Proteins Could Be the Next Frontier in Cancer Therapy.Cancer research · 2020Review
- Interactions of high mobility group box protein 1 (HMGB1) with nucleic acids: Implications in DNA repair and immune responses.DNA repair · 2019Review
- Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability.Molecular cell · 2019Article
- A novelBlood · 2019Article
- Connecting the Dots between Mechanosensitive Channel Abundance, Osmotic Shock, and Survival at Single-Cell Resolution.Journal of bacteriology · 2018Article
- Effect of transcription factor resource sharing on gene expression noise.PLoS computational biology · 2017Article
- Single-molecule studies of high-mobility group B architectural DNA bending proteins.Biophysical reviews · 2017Review
- Real-time analysis of RAG complex activity in V(D)J recombination.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The recombination-activating gene products, RAG1 and RAG2, initiate V(D)J recombination during lymphocyte development by cleaving DNA adjacent to conserved recombination signal sequences (RSSs). The reaction involves DNA binding, synapsis, and cleavage at two RSSs located on the same DNA molecule and results in the assembly of antigen receptor genes. We have developed single-molecule assays to examine RSS binding by RAG1/2 and their cofactor high-mobility group-box protein 1 (HMGB1) as they proceed through the steps of this reaction. These assays allowed us to observe in real time the individual molecular events of RAG-mediated cleavage. As a result, we are able to measure the binding statistics (dwell times) and binding energies of the initial RAG binding events and characterize synapse formation at the single-molecule level, yielding insights into the distribution of dwell times in the paired complex and the propensity for cleavage on forming the synapse. Interestingly, we find that the synaptic complex has a mean lifetime of roughly 400 s and that its formation is readily reversible, with only ∼40% of observed synapses resulting in cleavage at consensus RSS binding sites.
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Registered trials
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