RAG2 and XLF/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair - Institut Pasteur Access content directly
Journal Articles Nature Communications Year : 2016

RAG2 and XLF/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair

Abstract

XRCC4-like factor (XLF) functions in classical non-homologous end-joining (cNHEJ) but is dispensable for the repair of DNA double-strand breaks (DSBs) generated during V(D)J recombination. A long-standing hypothesis proposes that, in addition to its canonical nuclease activity, the RAG1/2 proteins participate in the DNA repair phase of V(D)J recombination. Here we show that in the context of RAG2 lacking the C-terminus domain (Rag2 c/c mice), XLF deficiency leads to a profound lymphopenia associated with a severe defect in V(D)J recombination and, in the absence of p53, increased genomic instability at V(D)J sites. In addition, Rag2 c/c XLF À/ À p53 À / À mice develop aggressive pro-B cell lymphomas bearing complex chromosomal translocations and gene amplifications involving Igh and c-myc/pvt1 loci. Our results reveal an unanticipated functional interplay between the RAG complex and XLF in repairing RAG-induced DSBs and maintaining genome integrity during antigen receptor gene assembly.
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pasteur-01295756 , version 1 (31-03-2016)

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Chloé Lescale, Vincent Abramowski, Marie Bedora-Faure, Valentine Murigneux, Gabriella Vera, et al.. RAG2 and XLF/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair. Nature Communications, 2016, 7, pp.Article number:10529. ⟨10.1038/ncomms10529⟩. ⟨pasteur-01295756⟩
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