| First Author | Rommel PC | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 3 | Pages | 815-831 |
| PubMed ID | 28179379 | Mgi Jnum | J:241225 |
| Mgi Id | MGI:5898171 | Doi | 10.1084/jem.20161638 |
| Citation | Rommel PC, et al. (2017) RAG1/2 induces genomic insertions by mobilizing DNA into RAG1/2-independent breaks. J Exp Med 214(3):815-831 |
| abstractText | The RAG recombinase (RAG1/2) plays an essential role in adaptive immunity by mediating V(D)J recombination in developing lymphocytes. In contrast, aberrant RAG1/2 activity promotes lymphocyte malignancies by causing chromosomal translocations and DNA deletions at cancer genes. RAG1/2 can also induce genomic DNA insertions by transposition and trans-V(D)J recombination, but only few such putative events have been documented in vivo. We used next-generation sequencing techniques to examine chromosomal rearrangements in primary murine B cells and discovered that RAG1/2 causes aberrant insertions by releasing cleaved antibody gene fragments that subsequently reintegrate into DNA breaks induced on a heterologous chromosome. We confirmed that RAG1/2 also mobilizes genomic DNA into independent physiological breaks by identifying similar insertions in human lymphoma and leukemia. Our findings reveal a novel RAG1/2-mediated insertion pathway distinct from DNA transposition and trans-V(D)J recombination that destabilizes the genome and shares features with reported oncogenic DNA insertions. |
