Cell cycle-dependent recruitment of telomerase RNA and Cajal bodies to human telomeres
Cell cycle-dependent recruitment of telomerase RNA and Cajal bodies to human telomeres
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DOI：
10.1091/mbc.e05-09-0904
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发表时间：
2006-02-01
影响因子：
3.3
通讯作者：
Kiss, T
中科院分区：
文献类型：
--
作者：
Jády, BE;Richard, P;Kiss, T
端粒酶是一种核糖核蛋白酶，通过在染色体末端添加端粒序列重复来抵消复制端粒的侵蚀。尽管端粒酶在端粒合成中起着很好的作用，但尚未在端粒中检测到端粒酶。人类端粒酶（hTR）的RNA成分存在于间期癌细胞的核质Cajal小体（CBs）中。在这里，原位杂交表明，在人HeLa和Hep2 S期细胞中，hTR除了在CBs中积累外，还特异性地集中在一些端粒上，这些端粒也积累了TRF1和TRF2端粒标记蛋白。令人惊讶的是，积累hTR的端粒在没有染色质变性的情况下表现出对原位寡核苷酸杂交的极大可及性，这表明它们代表了HeLa端粒的一个结构独特的小子集。此外，我们证明超过25%的积累hTR的端粒与CBs共定位。延时荧光显微镜显示，在S期细胞核质中移动的CBs与端粒短暂结合10-40分钟。我们的数据提出了一种有趣的可能性，即CBs可能将hTR传递到端粒和/或可能在端粒维护的其他方面发挥作用。
Telomerase is a ribonucleoprotein enzyme that counteracts replicative telomere erosion by adding telomeric sequence repeats onto chromosome ends. Despite its well-established role in telomere synthesis, telomerase has not yet been detected at telomeres. The RNA component of human telomerase (hTR) resides in the nucleoplasmic Cajal bodies (CBs) of interphase cancer cells. Here, in situ hybridization demonstrates that in human HeLa and Hep2 S phase cells, besides accumulating in CBs, hTR specifically concentrates at a few telomeres that also accumulate the TRF1 and TRF2 telomere marker proteins. Surprisingly, telomeres accumulating hTR exhibit a great accessibility for in situ oligonucleotide hybridization without chromatin denaturation, suggesting that they represent a structurally distinct, minor subset of HeLa telomeres. Moreover, we demonstrate that more than 25% of telomeres accumulating hTR colocalize with CBs. Time-lapse fluorescence microscopy demonstrates that CBs moving in the nucleoplasm of S phase cells transiently associate for 10-40 min with telomeres. Our data raise the intriguing possibility that CBs may deliver hTR to telomeres and/or may function in other aspects of telomere maintenance.