TELOMERASE ACTIVITY AND RADIATION SENSITIVITY

已经提出了端粒重复序列和端粒末端 转移酶(端粒酶)可能影响电离诱变 辐射。间质端粒重复序列被认为是 据报道，辐射敏感的脆弱部位和端粒酶 断裂的染色体末端，阻止它们的修复和促进 染色体终止化或重组。我们一直在描述一个 携带逆转录病毒gpt的中国仓鼠卵巢细胞株 航天飞机载体已经稳定整合。这个通常稳定的基因座在 T5细胞对电离后的缺失突变非常敏感 辐射暴露。该基因还显示了一个相对变异系数为3的let反应。 对于粒子来说。对整合地点的分析已经确定了区域 T2AG3的端粒重复gpt基因的3-启动子和5-引子。这个 这些研究的目标是确定端粒重复的作用 序列和端粒酶与辐射敏感性和基因组稳定性 使用该gpt轨迹作为模型系统。我们计划测试以下内容 假设：(L)在GPT整合中发现的端粒重复序列 通过以下方式将站点添加到载体或向载体整合站点 整合之前或整合期间的端粒酶，(2)这些端粒序列 使载体整合部位成为辐射敏感部位，以及(3) 端粒作为辐射敏感的脆弱部位，通过作为一个 进一步端粒酶作用和染色体终止化的位置或通过 提供重复结构以促进辐射诱导的复合。 这些研究应该会加深我们对 端粒酶和间质端粒序列在遗传病和 帮助更好地定义与环境相关的潜在风险 暴露在低LET和高LET辐射下。

It has been proposed that telomere repeat sequences and telomere terminal transferase (telomerase) may influence mutation induction by ionizing radiation. Interstitial telomere repeat sequences are thought to be radiation-sensitive fragile sites, and telomerase has been reported to cap the ends of broken chromosomes, preventing their repair and promoting chromosome terminalization or recombination. We have been characterizing a Chinese hamster ovary cell line into which a gpt containing retroviral shuttle vector has been stably integrated. This normally stable locus in T5 cells is very sensitive to deletion mutation following ionizing radiation exposure. The gene also shows an LET response with an RBE of 3 for a particles. Analysis of the integration site has identified regions of T2AG3 telomere repeats both 3-prime and 5-prime to the gpt gene. The goal of these studies is to establish the role of telomere repeat sequences and telomerase in radiation sensitivity and genomic stability using this gpt locus as a model system. We plan to test the following hypotheses: (l) the telomere repeat sequences found at the gpt integration site were added to the vector or to the vector integration site by telomerase prior to or during integration, (2) these telomeric sequences have made the vector integration site a radiation-sensitive site, and (3) telomeres act as radiation-sensitive fragile sites by either serving as a site for further telomerase action and chromosome terminalization or by providing repeat structures to facilitate radiation-induced recombination. These studies should further our understanding of the roles that telomerase and interstitial telomere sequences play in genetic disease and help to better define the potential risks associated with environmental exposures to both low- and high-LET radiations.