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© Sol-Foulon N.,Prévost M.C.,Schwartz O., Panaud J.M.
Particules du virus du Sida (VIH) bourgeonnant à la surface d'un lymphocyte T CD4. Microscopie electronique à balayage. Image colorisée. Coloured scanning electron micrograph (SEM) of AIDS virus particles at the surface of a lymphocyte T CD4 .
Publication : Nucleic acids research

RAG2 mutants alter DSB repair pathway choice in vivo and illuminate the nature of ‘alternative NHEJ’

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nucleic acids research - 20 Apr 2014

Gigi V, Lewis S, Shestova O, Mijušković M, Deriano L, Meng W, Luning Prak ET, Roth DB

Link to Pubmed [PMID] – 24753404

Nucleic Acids Res. 2014 Jun;42(10):6352-64

DNA double-stranded breaks (DSBs) can be repaired by several mechanisms, including classical NHEJ (c-NHEJ) and a poorly defined, error-prone process termed alternative NHEJ (a-NHEJ). How cells choose between these alternatives to join physiologic DSBs remains unknown. Here, we show that deletion of RAG2’s C-terminus allows a-NHEJ to repair RAG-mediated DSBs in developing lymphocytes from both c-NHEJ-proficient and c-NHEJ-deficient mice, demonstrating that the V(D)J recombinase influences repair pathway choice in vivo. Analysis of V(D)J junctions revealed that, contrary to expectation, junctional characteristics alone do not reliably distinguish between a-NHEJ and c-NHEJ. These data suggest that a-NHEJ is not necessarily mutagenic, and may be more prevalent than previously appreciated. Whole genome sequencing of a lymphoma arising in a p53(-/-) mouse bearing a C-terminal RAG2 truncation reveals evidence of a-NHEJ and also of aberrant recognition of DNA sequences resembling RAG recognition sites.

http://www.ncbi.nlm.nih.gov/pubmed/24753404