Telomerase maintains telomere structure in normal human cells
Telomerase maintains telomere structure in normal human cells
复制标题
DOI：
10.1016/s0092-8674(03)00550-6
复制
发表时间：
2003-07-25
期刊：
影响因子：
64.5
通讯作者：
Hahn, WC
中科院分区：
文献类型：
--
作者：
Masutomi, K;Yu, EY;Hahn, WC
在正常的人类细胞中，端粒随着细胞分裂的连续轮次而缩短，并且永生化与端粒长度的稳定性相关。这些观察结果表明，人类癌细胞在很大程度上通过端粒酶表达的非法激活实现永生化。在这里，我们证明了限速端粒酶催化亚基hTERT表达在循环原发性衰老的人成纤维细胞，以前认为缺乏hTERT表达和端粒酶活性。正常人类细胞中端粒酶活性的破坏减缓细胞增殖，限制细胞寿命，并改变3'单链端粒突出端的维持，而不改变总体端粒缩短的速率。总之，这些观察结果支持这样的观点，即端粒酶和端粒结构在正常人类细胞中受到动态调节，并且端粒长度本身不太可能触发进入复制性衰老。
In normal human cells, telomeres shorten with successive rounds of cell division, and immortalization correlates with stabilization of telomere length. These observations suggest that human cancer cells achieve immortalization in large part through the illegitimate activation of telomerase expression. Here, we demonstrate that the rate-limiting telomerase catalytic subunit hTERT is expressed in cycling primary presenescent human fibroblasts, previously believed to lack hTERT expression and telomerase activity. Disruption of telomerase activity in normal human cells slows cell proliferation, restricts cell lifespan, and alters the maintenance of the 3' single-stranded telomeric overhang without changing the rate of overall telomere shortening. Together, these observations support the view that telomerase and telomere structure are dynamically regulated in normal human cells and that telomere length alone is unlikely to trigger entry into replicative senescence.