Londoño-Vallejo J Arturo, Der-Sarkissian Héra, Cazes Lucien, Bacchetti Silvia, Reddel Roger R
Institut National de la Santé et de la Recherche Médicale, Paris, France.
Cancer Res. 2004 Apr 1;64(7):2324-7. doi: 10.1158/0008-5472.can-03-4035.
Telomere maintenance activity is a hallmark of cancer. In some telomerase-negative tumors, telomeres become lengthened by alternative lengthening of telomeres (ALT), a recombination-mediated DNA replication process in which telomeres use other telomeric DNA as a copy template. Using chromosome orientation fluorescence in situ hybridization, we found that postreplicative exchange events involving a telomere and another TTAGGG-repeat tract occur at remarkably high frequencies in ALT cells (range 28-280/100 metaphases) and rarely or never in non-ALT cells, including cell lines with very long telomeres. Like the ALT phenotype itself, the telomeric exchanges were not suppressed when telomerase was activated in ALT cells. These exchanges are telomere specific because there was no correlation with sister chromatid exchange rates at interstitial locations, and they were not observed in non-ALT Bloom syndrome cells with very high sister chromatid exchange rates.
端粒维持活性是癌症的一个标志。在一些端粒酶阴性肿瘤中，端粒通过端粒替代延长（ALT）而延长，这是一种重组介导的DNA复制过程，其中端粒使用其他端粒DNA作为复制模板。利用染色体定向荧光原位杂交技术，我们发现涉及一个端粒和另一个TTAGGG重复序列的复制后交换事件在ALT细胞中发生的频率非常高（范围为28 - 280/100个中期），而在非ALT细胞中很少发生或从未发生，包括端粒很长的细胞系。与ALT表型本身一样，当在ALT细胞中激活端粒酶时，端粒交换并未受到抑制。这些交换是端粒特异性的，因为它们与间期位置的姐妹染色单体交换率无关，并且在姐妹染色单体交换率非常高的非ALT布卢姆综合征细胞中未观察到。
