Alternative lengthening of telomeres is characterized by high rates of telomeric exchange
Alternative lengthening of telomeres is characterized by high rates of telomeric exchange
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DOI：
10.1158/0008-5472.can-03-4035
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发表时间：
2004-04-01
期刊：
影响因子：
11.2
通讯作者：
Reddel, RR
中科院分区：
文献类型：
--
作者：
Londoño-Vallejo, JA;Der-Sarkissian, H;Reddel, RR
端粒维持活动是癌症的一个标志。在一些端粒酶阴性的肿瘤中，端粒通过交替延长端粒(ALT)而延长，ALT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。利用染色体定位荧光原位杂交，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(范围28-280/100中期)中发生的频率非常高，而在非ALT细胞中很少或从不发生，包括端粒非常长的细胞系。与ALT表型本身一样，当ALT细胞中的端粒酶被激活时，端粒交换并未受到抑制。这些交换是端粒特异的，因为它们与间质部位的姐妹染色单体交换率没有相关性，而且在姐妹染色单体交换率非常高的非ALT Bloom综合征细胞中也没有观察到。
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.