Tomlinson Rebecca L, Ziegler Tania D, Supakorndej Teerawit, Terns Rebecca M, Terns Michael P
Departments of Biochemistry and Molecular Biology and Genetics, University of Georgia, Athens, GA 30602, USA.
Mol Biol Cell. 2006 Feb;17(2):955-65. doi: 10.1091/mbc.e05-09-0903. Epub 2005 Dec 7.
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.
端粒酶在S期合成人类染色体末端的端粒。本文给出的结果表明，端粒酶活性可能受人类细胞中该酶关键组分的核内运输调控。我们检测了内源性人类端粒酶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个关键组分聚集在与端粒分离的核内位点。然而，在S期，hTR和hTERT均特异性地被招募到端粒亚群。端粒酶定位于端粒是动态的，在S期中期达到峰值。我们还发现，在S期hTR和hTERT均与核仁及卡哈尔体存在复杂的关联，这表明这两种结构均参与端粒酶的生物合成及运输。我们的结果首次观察到人类端粒酶定位于端粒，并为人类细胞中端粒合成的细胞周期依赖性调控提供了一种机制。
