A two-step model for senescence triggered by a single critically short telomere.
A two-step model for senescence triggered by a single critically short telomere.
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衰老的两步模型由单个急速端粒触发。
DOI：
10.1038/ncb1911
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发表时间：
2009-08
影响因子：
21.3
通讯作者：
Teixeira, M. Teresa
中科院分区：
文献类型：
--
作者：
Abdallah, Pauline;Luciano, Pierre;Runge, Kurt W.;Lisby, Michael;Geli, Vincent;Gilson, Eric;Teixeira, M. Teresa
端粒保护染色体末端免于融合和降解。在没有特定端粒延长机制的情况下，它们的DNA随着每一轮复制而逐渐缩短，导致复制性衰老。在这里，我们表明，端粒缺失细胞轴承一个非常短的端粒衰老较早，表明最短的端粒长度是一个主要的决定因素的衰老开始。我们进一步表明，Mec 1 p/ATR特别识别导致加速衰老的单个非常短的端粒。引人注目的是，在进入衰老之前，细胞分裂了几代，尽管它们缩短的端粒被完全侵蚀。这种衰老前的生长需要RAD 52和MMS 1，并且没有证据表明主要的端粒间重组。我们提出，在端粒酶的情况下，一个非常短的端粒首先维持在一个前信号状态的RAD 52/MMS 1依赖性途径，然后切换到一个信号状态，导致衰老通过Mec 1 p依赖性检查点。
The telomeres protect chromosome ends from fusion and degradation. In the absence of a specific telomere elongation mechanism, their DNA progressively shortens with every round of replication leading to replicative senescence. Here, we show that telomerase-deficient cells bearing a single very short telomere senesce earlier, demonstrating that length of the shortest telomere is a major determinant of the onset of senescence. We further show that Mec1p/ATR recognises specifically the single very short telomere causing the accelerated senescence. Strikingly, before entry into senescence, cells divide for some generations despite a complete erosion of their shortened telomeres. This pre-senescence growth requires RAD52 and MMS1 and there is no evidence for major inter-telomeric recombination. We propose that, in the absence of telomerase, a very short telomere is first maintained in a pre-signalling state by a RAD52/MMS1 dependent pathway and then switches to a signalling state leading to senescence through a Mec1p-dependent checkpoint.
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影响因子：
3.8
作者：
Duro, Eris;Vaisica, Jessica A.;Rouse, John
通讯作者：
Rouse, John
影响因子：
11.4
作者：
Marcand, S;Brevet, V;Gilson, E
通讯作者：
Gilson, E
DOI：
10.1073/pnas.250475697
发表时间：
2000-12-05
影响因子：
11.1
作者：
Mallory, JC;Petes, TD
通讯作者：
Petes, TD
影响因子：
64.5
作者：
Hemann, MT;Strong, MA;Greider, CW
通讯作者：
Greider, CW
影响因子：
10.5
作者：
Bianchi, Alessandro;Shore, David
通讯作者：
Shore, David