| First Author | Gigi V | Year | 2014 |
| Journal | Nucleic Acids Res | Volume | 42 |
| Issue | 10 | Pages | 6352-64 |
| PubMed ID | 24753404 | Mgi Jnum | J:279820 |
| Mgi Id | MGI:6211113 | Doi | 10.1093/nar/gku295 |
| Citation | Gigi V, et al. (2014) RAG2 mutants alter DSB repair pathway choice in vivo and illuminate the nature of 'alternative NHEJ'. Nucleic Acids Res 42(10):6352-64 |
| abstractText | 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. |
