Cell cycle-regulated trafficking of human telomerase to telomeres
Cell cycle-regulated trafficking of human telomerase to telomeres
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DOI：
10.1091/mbc.e05-09-0903
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发表时间：
2006-02-01
影响因子：
3.3
通讯作者：
Terns, MP
中科院分区：
文献类型：
--
作者：
Tomlinson, RL;Ziegler, TD;Terns, MP
端粒酶在S期在人类染色体末端合成端粒。这里提出的结果表明，端粒酶活性可能是由人细胞中的酶的关键组分的核内运输调节。我们检测了内源性人端粒酶RNA（hTR）和端粒酶逆转录酶（hTERT）在HeLa宫颈癌细胞中的亚细胞定位。在细胞周期的大部分时间里，我们发现端粒酶的两种基本成分聚集在与端粒分离的核内位点。然而，在S期，hTR和hTERT都被特异性地募集到端粒的子集。端粒酶在端粒上的定位是动态的，在S期中期达到峰值。我们还发现，在S期，hTR和hTERT与核仁和Cajal小体的复杂关联，暗示这两种结构在端粒酶的生物发生和运输中。我们的研究结果标志着人类端粒酶在端粒的第一次观察，并提供了一个机制，细胞周期依赖性调控端粒合成在人类细胞。
Telomerase synthesizes telomeres at the ends of human chromosomes during S phase. The results presented here suggest that telomerase activity may be regulated by intranuclear trafficking of the key components of the enzyme in human cells. We examined the subcellular localization of endogenous human telomerase RNA (hTR) and telomerase reverse transcriptase (hTERT) in HeLa cervical carcinoma cells. Throughout most of the cell cycle, we found that the two essential components of telomerase accumulate at intranuclear sites separate from telomeres. However, during S phase, both hTR and hTERT are specifically recruited to subsets of telomeres. The localization of telomerase to telomeres is dynamic, peaking at mid-S phase. We also found complex associations of both hTR and hTERT with nucleoli and Cajal bodies during S phase, implicating both structures in the biogenesis and trafficking of telomerase. Our results mark the first observation of human telomerase at telomeres and provide a mechanism for the cell cycle-dependent regulation of telomere synthesis in human cells.