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Journal articles
Higher-order looping and nuclear organization of Tcra facilitate targeted rag cleavage and regulated rearrangement in recombination centers.
Abstract : V(D)J recombination is essential for generating a diverse array of B and T cell receptors that can recognize and combat foreign antigens. As with any recombination event, tight control is essential to prevent the occurrence of genetic anomalies that drive cellular transformation. One important aspect of regulation is directed targeting of the RAG recombinase. Indeed, RAG accumulates at the 3' end of individual antigen receptor loci poised for rearrangement; however, it is not known whether focal binding is involved in regulating cleavage, and what mechanisms lead to enrichment of RAG in this region. Here, we show that monoallelic looping out of the 3' end of the T cell receptor α (Tcra) locus, coupled with transcription and increased chromatin/nuclear accessibility, is linked to focal RAG binding and ATM-mediated regulation of monoallelic cleavage on looped-out 3' regions. Our data identify higher-order loop formation as a key determinant of directed RAG targeting and the maintenance of genome stability.
Keywords :
*V(D)J Recombination
Alleles
Animals
Ataxia Telangiectasia Mutated Proteins
Cell Cycle Proteins/metabolism
Cell Nucleus/metabolism
DNA-Binding Proteins/genetics/*metabolism
DNA Damage
Genetic Loci
Genomic Instability
Histones/genetics
Homeodomain Proteins/genetics/*metabolism
Mice
Inbred C57BL
Inbred CBA
Knockout
Protein-Serine-Threonine Kinases/metabolism
Receptors
Antigen
T-Cell
alpha-beta/genetics/*metabolism
Tumor Suppressor Proteins/metabolism
Cited literature [43 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-01471693
Contributor : Anne Lassailly-Bondaz Connect in order to contact the contributor
Submitted on : Monday, February 20, 2017 - 11:41:43 AM
Last modification on : Thursday, April 7, 2022 - 10:10:32 AM
Long-term archiving on: : Sunday, May 21, 2017 - 1:22:58 PM
Contributor : Anne Lassailly-Bondaz Connect in order to contact the contributor
Submitted on : Monday, February 20, 2017 - 11:41:43 AM
Last modification on : Thursday, April 7, 2022 - 10:10:32 AM
Long-term archiving on: : Sunday, May 21, 2017 - 1:22:58 PM
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Publication funded by an institution
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Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License