ArticleMolecular and cellular biology1999
Mechanistic basis for coding end sequence effects in the initiation of V(D)J recombination.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Building a neural network model to define DNA sequence specificity in V(D)J recombination.Nucleic acids research · 2025Article
- Locus folding mechanisms determine modes of antigen receptor gene assembly.The Journal of experimental medicine · 2024Article
- An updated definition of V(D)J recombination signal sequences revealed by high-throughput recombination assays.Nucleic acids research · 2022Article
- Sequence-dependent dynamics of synthetic and endogenous RSSs in V(D)J recombination.Nucleic acids research · 2020Article
- Genome Topology Control of Antigen Receptor Gene Assembly.Journal of immunology (Baltimore, Md. : 1950) · 2020Review
- Article
- Synapsis alters RAG-mediated nicking at Tcrb recombination signal sequences: implications for the “beyond 12/23” rule.Molecular and cellular biology · 2014Article
- Unifying model for molecular determinants of the preselection Vβ repertoire.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- A Novel Quantitative Fluorescent Reporter Assay for RAG Targets and RAG Activity.Frontiers in immunology · 2013Article
- Skewed primary Igκ repertoire and V-J joining in C57BL/6 mice: implications for recombination accessibility and receptor editing.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Recombination centres and the orchestration of V(D)J recombination.Nature reviews. Immunology · 2011Review
- Cytosines, but not purines, determine recombination activating gene (RAG)-induced breaks on heteroduplex DNA structures: implications for genomic instability.The Journal of biological chemistry · 2010Article
- H3K4me3 stimulates the V(D)J RAG complex for both nicking and hairpinning in trans in addition to tethering in cis: implications for translocations.Molecular cell · 2009Article
- Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation.Blood · 2009Article
- A role for DNA polymerase mu in the emerging DJH rearrangements of the postgastrulation mouse embryo.Molecular and cellular biology · 2009Article
- Article
- A RAG1 mutation found in Omenn syndrome causes coding flank hypersensitivity: a novel mechanism for antigen receptor repertoire restriction.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination.Molecular and cellular biology · 2007Article
- Fluorescence resonance energy transfer analysis of recombination signal sequence configuration in the RAG1/2 synaptic complex.Molecular and cellular biology · 2007Article
- The structure-specific nicking of small heteroduplexes by the RAG complex: implications for lymphoid chromosomal translocations.DNA repair · 2007Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
V(D)J recombination is directed by recombination signal sequences. However, the flanking coding end sequence can markedly affect the frequency of the initiation of V(D)J recombination in vivo. Here we demonstrate that the coding end sequence effect can be qualitatively and quantitatively recapitulated in vitro with purified RAG proteins. We find that coding end sequence specifically affects the nicking step, which is the first biochemical step in RAG-mediated cleavage. The subsequent hairpin formation step is not affected by the coding end sequence. Furthermore, the coding end sequence effect can be ablated by prenicking the substrate, indicating that the coding end effect is specific to the nicking step. In reactions in which both 12- and 23-substrates are present, a suboptimal coding end sequence on one signal can slow down hairpin formation at the partner signal, a result consistent with models in which coordination between the signals occurs at the hairpin formation step. The coding end sequence effect on nicking and the coupling of the 12- and 23-substrates explains how hairpin formation can be rate limiting for some 12/23 pairs, whereas nicking can be rate limiting when low-efficiency coding end sequences are involved.
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