Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres.
Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres.
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DOI：
10.1038/nsmb.1897
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发表时间：
2010-10
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
作者：
在原代细胞的复制老化过程中，发生形态学转变，表达模式改变，染色质发生全局变化。在这里，我们表明慢性损伤信号，可能是由端粒加工引起的，影响组蛋白的表达并导致其耗尽。询问组蛋白和组蛋白伴侣的丰度和细胞周期表达揭示了复制性衰老过程中组蛋白生物合成的缺陷。同时，表观遗传标记在细胞周期的各个阶段重新分布，DNA损伤反应（DDR）机制被激活。年龄依赖性重编程影响端粒染色质本身，其逐渐不稳定，导致端粒相关的DDR信号随着每个连续的细胞周期而增强。我们提出了一种机制，其中端粒的结构和表观遗传完整性的变化影响核心组蛋白及其伴侣，强制执行一个自我永存的全球表观遗传变化的途径，最终导致衰老。
During replicative aging of primary cells morphological transformations occur, the expression pattern is altered and chromatin changes globally. Here we show that chronic damage signals, likely caused by telomere processing, impact expression of histones and lead to their depletion. Interrogation of the abundance and cell cycle expression of histones and histone chaperones revealed defects in histone biosynthesis during replicative aging. Simultaneously, epigenetic marks were redistributed across the phases of the cell cycle and the DNA damage response (DDR) machinery was activated. The age-dependent reprogramming affected telomeric chromatin itself, which was progressively destabilized, resulting in a boost of the telomere associated DDR signal with each successive cell cycle. We propose a mechanism where changes in the structural and epigenetic integrity of telomeres impact core histones and their chaperones, enforcing a self-perpetuating pathway of global epigenetic changes that ultimately leads to senescence.
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影响因子：
56.9
作者：
Bunz, F;Dutriaux, A;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
16
作者：
Altaf, Mohammed;Utley, Rhea T.;Cote, Jacques
通讯作者：
Cote, Jacques
影响因子：
16
作者：
Jasencakova, Zuzana;Scharf, Annette N. D.;Groth, Anja
通讯作者：
Groth, Anja
DOI：
10.1073/pnas.1635158100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Hoek, M;Stillman, B
通讯作者：
Stillman, B
影响因子：
9.2
作者：
Feng, Q;Wang, HB;Zhang, Y
通讯作者：
Zhang, Y