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

Lescale, Chloe, Abramowski, Vincent, Bedora-Faure, Marie, Murigneux, Valentine, Vera, Gabriella, Roth, David B., Revy, Patrick, de Villartay, Jean-Pierre and Deriano, Ludovic (2016) RAG2 and XLF/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair. Nature Communications, 7 10529.1-10529.13. doi:10.1038/ncomms10529


Author Lescale, Chloe
Abramowski, Vincent
Bedora-Faure, Marie
Murigneux, Valentine
Vera, Gabriella
Roth, David B.
Revy, Patrick
de Villartay, Jean-Pierre
Deriano, Ludovic
Title RAG2 and XLF/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2016-02-01
Sub-type Article (original research)
DOI 10.1038/ncomms10529
Open Access Status DOI
Volume 7
Start page 10529.1
End page 10529.13
Total pages 13
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Formatted 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 (Rag2c/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, Rag2c/c XLF-/- p53-/- 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
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