Human telomeres maintain their overhang length at senescence
Human telomeres maintain their overhang length at senescence
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DOI：
10.1128/mcb.25.6.2158-2168.2005
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发表时间：
2005-03-01
影响因子：
5.3
通讯作者：
Wright, WE
中科院分区：
文献类型：
--
作者：
Chai, WH;Shay, JW;Wright, WE
正常的人类细胞在经过有限数量的群体倍增后进入复制性衰老。引发生长停滞的确切分子机制尚不清楚。最近一份关于衰老细胞中富含g的3‘端粒悬垂消失的报告提出了一种假设，即富含g的3’端粒悬垂的消失是触发衰老的分子信号。在这里，我们描述了一种定量测定方法来测量培养细胞中富含g的3'端粒悬垂的长度。使用这种方法和传统的非变性杂交方法来测量富含g的悬量，我们发现正常的人类成纤维细胞在衰老时可以保持它们的悬量。此外，当p53和Rb失活后，细胞绕过衰老时，并不会失去它们的悬垂。因此，我们得出结论，悬垂长度的整体减少不是触发复制性衰老的分子信号。
Normal human cells in culture enter replicative senescence after a finite number of population doublings. The exact molecular mechanisms triggering the growth arrest are poorly understood. A recent report on the disappearance of the G-rich 3' telomeric overhang in senescent cells led to the hypothesis that loss of the 3' G-rich overhang is the molecular signal that triggers senescence. Here, we describe a quantitative assay to measure the length of the G-rich 3' telomeric overhangs from cultured cells. Using both this assay and the conventional nondenaturing hybridization assay for measuring G-rich overhangs, we show that normal human fibroblasts can maintain their overhangs at senescence. Furthermore, cells do not lose their overhangs when they bypass senescence after the inactivation of p53 and Rb. We thus conclude that a global reduction in overhang length is not the molecular signal that triggers replicative senescence.