Initiation of V(D)J recombination by Dbeta-associated recombination signal sequences: a critical control point in TCRbeta gene assembly.

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 d...

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Autores principales:	Don-Marc Franchini, Touati Benoukraf, Sébastien Jaeger, Pierre Ferrier, Dominique Payet-Bornet
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c61a47abea8d479f9a74f51de5866ca0
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spelling	oai:doaj.org-article:c61a47abea8d479f9a74f51de5866ca02021-11-25T06:17:08ZInitiation of V(D)J recombination by Dbeta-associated recombination signal sequences: a critical control point in TCRbeta gene assembly.1932-620310.1371/journal.pone.0004575https://doaj.org/article/c61a47abea8d479f9a74f51de5866ca02009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19238214/?tool=EBIhttps://doaj.org/toc/1932-6203T 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.Don-Marc FranchiniTouati BenoukrafSébastien JaegerPierre FerrierDominique Payet-BornetPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 2, p e4575 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Don-Marc Franchini Touati Benoukraf Sébastien Jaeger Pierre Ferrier Dominique Payet-Bornet Initiation of V(D)J recombination by Dbeta-associated recombination signal sequences: a critical control point in TCRbeta gene assembly.
description	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.
format	article
author	Don-Marc Franchini Touati Benoukraf Sébastien Jaeger Pierre Ferrier Dominique Payet-Bornet
author_facet	Don-Marc Franchini Touati Benoukraf Sébastien Jaeger Pierre Ferrier Dominique Payet-Bornet
author_sort	Don-Marc Franchini
title	Initiation of V(D)J recombination by Dbeta-associated recombination signal sequences: a critical control point in TCRbeta gene assembly.
title_short	Initiation of V(D)J recombination by Dbeta-associated recombination signal sequences: a critical control point in TCRbeta gene assembly.
title_full	Initiation of V(D)J recombination by Dbeta-associated recombination signal sequences: a critical control point in TCRbeta gene assembly.
title_fullStr	Initiation of V(D)J recombination by Dbeta-associated recombination signal sequences: a critical control point in TCRbeta gene assembly.
title_full_unstemmed	Initiation of V(D)J recombination by Dbeta-associated recombination signal sequences: a critical control point in TCRbeta gene assembly.
title_sort	initiation of v(d)j recombination by dbeta-associated recombination signal sequences: a critical control point in tcrbeta gene assembly.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/c61a47abea8d479f9a74f51de5866ca0
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Initiation of V(D)J recombination by Dbeta-associated recombination signal sequences: a critical control point in TCRbeta gene assembly.

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