| Title |
Off-Target V(D)J Recombination Drives Lymphomagenesis and Is Escalated by Loss of the Rag2 C Terminus
|
|---|---|
| Published in |
Cell Reports, September 2015
|
| DOI | 10.1016/j.celrep.2015.08.034 |
| Pubmed ID | |
| Authors | |
| Abstract |
Genome-wide analysis of thymic lymphomas from Tp53(-/-) mice with wild-type or C-terminally truncated Rag2 revealed numerous off-target, RAG-mediated DNA rearrangements. A significantly higher fraction of these errors mutated known and suspected oncogenes/tumor suppressor genes than did sporadic rearrangements (p < 0.0001). This tractable mouse model recapitulates recent findings in human pre-B ALL and allows comparison of wild-type and mutant RAG2. Recurrent, RAG-mediated deletions affected Notch1, Pten, Ikzf1, Jak1, Phlda1, Trat1, and Agpat9. Rag2 truncation substantially increased the frequency of off-target V(D)J recombination. The data suggest that interactions between Rag2 and a specific chromatin modification, H3K4me3, support V(D)J recombination fidelity. Oncogenic effects of off-target rearrangements created by this highly regulated recombinase may need to be considered in design of site-specific nucleases engineered for genome modification. |
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X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 19% |
| Spain | 3 | 19% |
| Mexico | 2 | 13% |
| France | 1 | 6% |
| Chile | 1 | 6% |
| Unknown | 6 | 38% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 15 | 94% |
| Science communicators (journalists, bloggers, editors) | 1 | 6% |
Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Ireland | 1 | 2% |
| Unknown | 58 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 12 | 20% |
| Researcher | 9 | 15% |
| Student > Master | 6 | 10% |
| Student > Bachelor | 4 | 7% |
| Professor | 4 | 7% |
| Other | 11 | 19% |
| Unknown | 13 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 18 | 31% |
| Agricultural and Biological Sciences | 17 | 29% |
| Immunology and Microbiology | 3 | 5% |
| Medicine and Dentistry | 3 | 5% |
| Computer Science | 2 | 3% |
| Other | 3 | 5% |
| Unknown | 13 | 22% |