Findings from previous studies have suggested that the telomerase system is involved in radiation-induced genomic instability. In this study, we investigated the involvement of telomerase in the development and processing of chromosomal damage at different cell cycle stages after irradiation of human fibroblasts. Several response criteria were investigated, including cell survival, chromosomal damage (using the micronucleus assay), G2-induced chromatid aberrations (using the conventional G2 assay as well as a chemically-induced premature chromosome condensation assay) and DNA double-strand breaks (DSBs; using γ-H2AX, 53BP1 and Rad51) in an isogenic pair of cell lines: BJ human foreskin fibroblasts and BJ1-hTERT, a telomerase-immortalized BJ cell line. To distinguish among G1, S and G2 phase, cells were co-immunostained for CENP-F and cyclin A, which are tightly regulated proteins in the cell cycle. After X-ray irradiation at doses in the range of 0.1-6 Gy, the results showed that for cell survival and micronuclei induction, where the overall effect is dominated by the cells in G1 and S phase, no difference was observed between the two cell types; in contrast, when radiation sensitivity at the G2 stage of the cell cycle was analyzed, a significantly higher number of chromatid-type aberrations (breaks and exchanges), and higher levels of γ-H2AX and of Rad51 foci were observed for the BJ cells compared to the BJ1-hTERT cells. Therefore, it can be concluded that telomerase appears to be involved in DNA DSB repair processes, mainly in the G2 phase. These data, taken overall, reinforce the notion that hTERT or other elements of the telomere/telomerase system may defend chromosome integrity in human fibroblasts by promoting repair in G2 phase of the cell cycle.

中文翻译：

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端粒酶在辐射诱导的基因组不稳定中的作用。

先前研究的发现表明端粒酶系统参与了辐射诱导的基因组不稳定。在这项研究中，我们调查了人类成纤维细胞照射后不同细胞周期阶段端粒酶参与染色体损伤的发展和过程。研究了几种反应标准，包括细胞存活率，染色体损伤（使用微核测定），G2诱导的染色体畸变（使用常规的G2测定以及化学诱导的早熟染色体凝缩测定）和DNA双链断裂（DSB） ；使用γ-H2AX，53BP1和Rad51）在一对同基因的细胞系中：BJ人包皮成纤维细胞和BJ1-hTERT（端粒酶永生化BJ细胞系）。为了区分G1，S和G2期，对细胞进行了CENP-F和细胞周期蛋白A的免疫共染色，在细胞周期中是严格调节的蛋白质。在0.1-6 Gy的剂量范围内进行X射线辐照后，结果表明，对于细胞存活和微核诱导而言，总体作用主要由G1和S期细胞决定，两个细胞之间没有发现差异类型; 相反，当分析细胞周期G2阶段的辐射敏感性时，与BJ细胞相比，观察到的染色单体型畸变（断裂和交换）明显多得多，并且γ-H2AX和Rad51病灶的水平也更高。到BJ1-hTERT细胞。因此，可以得出结论，端粒酶似乎与DNA DSB修复过程有关，主要在G2期。这些数据总的来说，