ArticleMolecular and cellular biology2007
The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination.
Article in Molecular and cellular biology, 2007. 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, 31 citations in OpenAlex.
- HTS and scRNA-seq revealed that the location and RSS quality of the mammalian TRBV and TRBJ genes impact biased rearrangement.BMC genomics · 2024Article
- 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
- Cracking the DNA Code for V(D)J Recombination.Molecular cell · 2018Article
- Synapsis alters RAG-mediated nicking at Tcrb recombination signal sequences: implications for the “beyond 12/23” rule.Molecular and cellular biology · 2014Article
- Crosstalk between transposase subunits during cleavage of the mariner transposon.Nucleic acids research · 2014Article
- Cooperative recruitment of HMGB1 during V(D)J recombination through interactions with RAG1 and DNA.Nucleic acids research · 2013Article
- Role of recombination activating genes in the generation of antigen receptor diversity and beyond.Immunology · 2012Review
- DNA double-strand breaks relieve USF-mediated repression of Dβ2 germline transcription in developing thymocytes.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- The center of accessibility: Dβ control of V(D)J recombination.Archivum immunologiae et therapiae experimentalis · 2010Review
- TCR beta feedback signals inhibit the coupling of recombinationally accessible V beta 14 segments with DJ beta complexes.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Base flipping in V(D)J recombination: insights into the mechanism of hairpin formation, the 12/23 rule, and the coordination of double-strand breaks.Molecular and cellular biology · 2009Article
- Recombination signal sequence-associated restriction on TCRdelta gene rearrangement affects the development of tissue-specific gammadelta T cells.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Mechanics of T cell receptor gene rearrangement.Current opinion in immunology · 2009Review
- Article
- Cis-regulatory elements and epigenetic changes control genomic rearrangements of the IgH locus.Advances in immunology · 2008Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The beyond 12/23 (B12/23) rule ensures inclusion of a Dbeta gene segment in the assembled T-cell receptor (TCR) beta variable region exon and is manifest by a failure of direct Vbeta-to-Jbeta gene segment joining. The restriction is enforced during the DNA cleavage step of V(D)J recombination by the recombination-activating gene 1 and 2 (RAG1/2) proteins and the recombination signal sequences (RSSs) flanking the TCRbeta gene segments. Nothing is known about the step(s) at which DNA cleavage is defective or how TCRbeta locus sequences contribute to these defects. To address this, we examined the steps of DNA cleavage by the RAG proteins using TCRbeta locus V, D, and J RSS oligonucleotide substrates. The results demonstrate that the B12/23 rule is enforced through slow nicking of Jbeta substrates and to some extent through poor synapsis of Vbeta and Jbeta substrates. Nicking is controlled largely by the coding flank and, unexpectedly, the RSS spacer, while synapsis is controlled primarily by the RSS nonamer. The results demonstrate that different Jbeta substrates are crippled at different steps of cleavage by distinct combinations of defects in the various DNA elements and strongly suggest that the DNA nicking step of V(D)J recombination can be rate limiting in vivo.
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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.