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© Deriano Lab / Institut Pasteur
Chromosomes métaphasiques d’une cellule lymphoïde cancéreuse présentant une amplification des gènes Igh et c-myc
Publication : Cell reports

Higher-order looping and nuclear organization of Tcra facilitate targeted rag cleavage and regulated rearrangement in recombination centers

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell reports - 14 Feb 2013

Chaumeil J, Micsinai M, Ntziachristos P, Deriano L, Wang JM, Ji Y, Nora EP, Rodesch MJ, Jeddeloh JA, Aifantis I, Kluger Y, Schatz DG, Skok JA

Link to Pubmed [PMID] – 23416051

Cell Rep 2013 Feb;3(2):359-70

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.

http://www.ncbi.nlm.nih.gov/pubmed/23416051