Enforced telomere elongation increases the sensitivity of human tumour cells to ionizing radiation

Abstract

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.