| First Author | Zhu C | Year | 2002 |
| Journal | Cell | Volume | 109 |
| Issue | 7 | Pages | 811-21 |
| PubMed ID | 12110179 | Mgi Jnum | J:77972 |
| Mgi Id | MGI:2183000 | Doi | 10.1016/s0092-8674(02)00770-5 |
| Citation | Zhu C, et al. (2002) Unrepaired DNA Breaks in p53-Deficient Cells Lead to Oncogenic Gene Amplification Subsequent to Translocations. Cell 109(7):811-21 |
| abstractText | Amplification of large genomic regions associated with complex translocations (complicons) is a basis for tumor progression and drug resistance. We show that pro-B lymphomas in mice deficient for both p53 and nonhomologous end-joining (NHEJ) contain complicons that coamplify c-myc (chromosome 15) and IgH (chromosome 12) sequences. While all carry a translocated (12;15) chromosome, coamplified sequences are located within a separate complicon that often involves a third chromosome. Complicon formation is initiated by recombination of RAG1/2-catalyzed IgH locus double-strand breaks with sequences downstream of c-myc, generating a dicentric (15;12) chromosome as an amplification intermediate. This recombination event employs a microhomology-based end-joining repair pathway, as opposed to classic NHEJ or homologous recombination. These findings suggest a general model for oncogenic complicon formation. |
