Fairlie Jennifer, Harrington Lea
Wellcome Trust Centre for Cell Biology and Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Mayfield Road, EH9 3JR Edinburgh, UK.
Wellcome Trust Centre for Cell Biology and Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Mayfield Road, EH9 3JR Edinburgh, UK; Institute for Research in Immunology and Cancer, Department of Medicine, University of Montreal, 2950 chemin de Polytechnique, Montreal, Canada H3T 1J4.
DNA Repair (Amst). 2015 Jan;25:54-9. doi: 10.1016/j.dnarep.2014.11.005. Epub 2014 Nov 24.
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 17kbp 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.
超过85%的人类癌症凭借端粒酶活性具备维持染色体末端（即端粒）的能力。功能性端粒的缺失与细胞存活不兼容，并且在多个模型系统中已证实抑制端粒酶是癌症治疗的一个可行靶点。由于人类肿瘤细胞通常维持较短的平衡端粒长度，我们想知道强制延长端粒对细胞存活会产生正面还是负面影响。我们发现，端粒延长超过一定长度会显著降低γ射线照射后细胞的克隆存活能力。对辐射的敏感性呈剂量依赖性，并且在端粒长度超过17千碱基对时增加，尽管所有染色体末端都保留了端粒DNA。这些数据表明，在存在基因毒性应激的情况下，最佳端粒长度可能会促进人类癌细胞的存活。
