ArticlePloS one2009
Initiation of V(D)J recombination by Dbeta-associated recombination signal sequences: a critical control point in TCRbeta gene assembly.
Article in PloS one, 2009. 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, 22 citations in OpenAlex.
- The recombinase activating genes: architects of immune diversity during lymphocyte development.Frontiers in immunology · 2023Review
- On the organization of human T-cell receptor loci: log-periodic distribution of T-cell receptor gene segments.Journal of the Royal Society, Interface · 2016Review
- RUNX1-dependent RAG1 deposition instigates human TCR-δ locus rearrangement.The Journal of experimental medicine · 2014Article
- Synapsis alters RAG-mediated nicking at Tcrb recombination signal sequences: implications for the “beyond 12/23” rule.Molecular and cellular biology · 2014Article
- DNA double-strand breaks relieve USF-mediated repression of Dβ2 germline transcription in developing thymocytes.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Recombination centres and the orchestration of V(D)J recombination.Nature reviews. Immunology · 2011Review
- 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
- Extensive analysis of D-J-C arrangements allows the identification of different mechanisms enhancing the diversity in sheep T cell receptor beta-chain repertoire.BMC genomics · 2010Article
- Promoter activity 5' of Dbeta2 is coordinated by E47, Runx1, and GATA-3.Molecular immunology · 2009Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell receptor (TCR) beta gene assembly by V(D)J recombination proceeds via successive Dbeta-to-Jbeta and Vbeta-to-DJbeta rearrangements. This two-step process is enforced by a constraint, termed beyond (B)12/23, which prohibits direct Vbeta-to-Jbeta rearrangements. However the B12/23 restriction does not explain the order of TCRbeta assembly for which the regulation remains an unresolved issue. The initiation of V(D)J recombination consists of the introduction of single-strand DNA nicks at recombination signal sequences (RSSs) containing a 12 base-pairs spacer. An RSS containing a 23 base-pairs spacer is then captured to form a 12/23 RSSs synapse leading to coupled DNA cleavage. Herein, we probed RSS nicks at the TCRbeta locus and found that nicks were only detectable at Dbeta-associated RSSs. This pattern implies that Dbeta 12RSS and, unexpectedly, Dbeta 23RSS initiate V(D)J recombination and capture their respective Vbeta or Jbeta RSS partner. Using both in vitro and in vivo assays, we further demonstrate that the Dbeta1 23RSS impedes cleavage at the adjacent Dbeta1 12RSS and consequently Vbeta-to-Dbeta1 rearrangement first requires the Dbeta1 23RSS excision. Altogether, our results provide the molecular explanation to the B12/23 constraint and also uncover a 'Dbeta1 23RSS-mediated' restriction operating beyond chromatin accessibility, which directs Dbeta1 ordered rearrangements.
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