Telomere fusion to chromosome breaks reduces oncogenic translocations and tumour formation
| Autor: | Baktiar O. Karim, Carol W. Greider, Ling Qi, Margaret A. Strong, David L. Huso |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Genome instability
Male Genotype DNA damage Chromosomal translocation Apoptosis Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Mice SCID Biology Protein Serine-Threonine Kinases medicine.disease_cause Gene Rearrangement T-Lymphocyte Lymphoma T-Cell Genomic Instability Translocation Genetic chemistry.chemical_compound Mice Transcription (biology) medicine Animals Telomerase Crosses Genetic In Situ Hybridization Fluorescence Cell Proliferation Mice Knockout B-Lymphocytes Models Genetic Tumor Suppressor Proteins Body Weight Spectral Karyotyping Age Factors Chromosome Breakage Cell Biology Gene rearrangement Neoplasms Experimental Telomere Survival Analysis Cell biology DNA-Binding Proteins Genes T-Cell Receptor chemistry Female Carcinogenesis DNA Neoplasm Transplantation |
| Zdroj: | Nature cell biology. 7(7) |
| ISSN: | 1465-7392 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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