Telomerase can act as a template- and RNA-independent terminal transferase
Telomerase can act as a template- and RNA-independent terminal transferase
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DOI：
10.1073/pnas.0502252102
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发表时间：
2005-07-12
影响因子：
11.1
通讯作者：
Leng, SY
中科院分区：
文献类型：
--
作者：
Lue, NF;Bosoy, D;Leng, SY
端粒酶是一种特殊的逆转录酶，它利用嵌入在RNA亚基中的模板来延长端粒重复序列的一条链。与其他聚合酶一样，端粒酶被认为使用一对二价金属离子(由三个天冬氨酸残基配位)来催化核苷酸加成。在这里，我们表明，在锰的存在下，酵母和人类端粒酶都可以切换到模板和RNA无关的DNA合成模式，实际上起到终端转移酶的作用。即使作为一种末端转移酶，酵母端粒酶仍然对底物5‘端富含GT的端粒样DNA保持着一种依赖物种的偏好。端粒酶的末端转移酶活性可能解释了端粒酶过度表达对细胞生理学的一些迄今无法解释的影响。
Telomerase is a special reverse transcriptase that extends one strand of the telomere repeat by using a template embedded in an RNA subunit. Like other polymerases, telomerase is believed to use a pair of divalent metal ions (coordinated by a triad of aspartic acid residues) for catalyzing nucleotide addition. Here we show that, in the presence of manganese, both yeast and human telomerase can switch to a template- and RNA-independent mode of DNA synthesis, acting in effect as a terminal transferase. Even as a terminal transferase, yeast telomerase retains a species-dependent preference for GT-rich, telomere-like DNA on the 5' end of the substrate. The terminal transferase activity of telomerase may account for some of the hitherto unexplained effects of telomerase overexpression on cell physiology.