Enforced telomere elongation increases the sensitivity of human tumour cells to ionizing radiation
| Autor: | Jennifer Fairlie, Lea Harrington |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Telomerase
Cell Survival DNA damage Cell Gamma irradiation Genotoxic Stress Biology Brief Communication PE plating efficiency SFE signal-free end Biochemistry Ionizing radiation CST CTC1 STN1 and TEN1 complex Q-FISH quantitative fluorescence in situ hybridization Telomere Homeostasis Neoplasms Tumor Cells Cultured medicine Humans Human tumour cells SV40 simian virus 40 Molecular Biology ANOVA analysis of variance ALT alternative lengthening of telomeres Chromosome Cell Biology Telomere Molecular biology TERT telomerase reverse transcriptase 3. Good health Cell biology Telomeres hTR human telomerase RNA medicine.anatomical_structure Gamma Rays PDL population doubling level TRF telomere restriction fragment DSB double-stranded DNA break SF survival fraction |
| Zdroj: | DNA Repair |
| ISSN: | 1568-7864 |
| DOI: | 10.1016/j.dnarep.2014.11.005 |
| Popis: | Highlights • Telomere elongation decreases human tumour cell viability after irradiation. • The longer the telomeres, the greater the sensitivity to sub-lethal irradiation. • Increased sensitivity to irradiation is independent of telomere signal-free ends. More than 85% of all human cancers possess the ability to maintain chromosome ends, or telomeres, by virtue of telomerase activity. Loss of functional telomeres is incompatible with survival, and telomerase inhibition has been established in several model systems to be a tractable target for cancer therapy. As human tumour cells typically maintain short equilibrium telomere lengths, we wondered if enforced telomere elongation would positively or negatively impact cell survival. We found that telomere elongation beyond a certain length significantly decreased cell clonogenic survival after gamma irradiation. Susceptibility to irradiation was dosage-dependent and increased at telomere lengths exceeding 17 kbp despite the fact that all chromosome ends retained telomeric DNA. These data suggest that an optimal telomere length may promote human cancer cell survival in the presence of genotoxic stress. |
| Databáze: | OpenAIRE |
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