| First Author | Qi L | Year | 2005 |
| Journal | Nat Cell Biol | Volume | 7 |
| Issue | 7 | Pages | 706-11 |
| PubMed ID | 15965466 | Mgi Jnum | J:100156 |
| Mgi Id | MGI:3587154 | Doi | 10.1038/ncb1276 |
| Citation | Qi L, et al. (2005) Telomere fusion to chromosome breaks reduces oncogenic translocations and tumour formation. Nat Cell Biol 7(7):706-11 |
| abstractText | Telomeres protect chromosome ends from fusion, degradation and recombination. Loss of telomere function has opposite effects on tumorigenesis: apoptosis, which inhibits tumour growth, and genomic instability, which accelerates tumour formation. Here we describe a new mechanism by which short telomeres inhibit tumorigenesis through interference with oncogenic translocations. In mice that are null for both ataxia-telangiectasia-mutated (Atm) and telomerase RNA (mTR), the first generation (G1) Atm-/- mTR-/- mice have a lower rate of tumour formation than Atm-/- mTR+/+ mice. These Atm-/- mTR-/- G1 tumours show no increase in either apoptosis or overall genomic instability. Strikingly, the tumours show a high fraction of translocations containing telomere signals at the translocation junctions. Translocations of the T-cell receptors on chromosome 14, which initiate tumorigenesis, were interrupted by fusion with telomeres. Telomere repeats were also detected at the translocation junctions in pre-malignant thymocytes. We propose that telomere fusion to DNA double-strand breaks competes with the generation of oncogenic translocations and thus reduces tumour formation. |
