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末端延伸:是什么使得端粒酶具有持续性,以及其重要性如何?

Adding to the ends: what makes telomerase processive and how important is it?

作者信息

Lue Neal F

机构信息

Department of Microbiology & Immunology, W. R. Hearst Microbiology Research Center, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.

出版信息

Bioessays. 2004 Sep;26(9):955-62. doi: 10.1002/bies.20093.

Abstract

Telomerase is a cellular reverse transcriptase responsible for telomere maintenance in most organisms. It does so by adding telomere repeats onto pre-existing ends using an integral RNA component as template. Compared to "prototypical" reverse transcriptases, telomerase is unique in being able to repetitively copy a short templating RNA segment, thus adding multiple copies of the repeat to the DNA substrate following a single binding event. This uniquely processive property hints at the intricate conformational alterations that the enzyme must choreograph during its reaction cycles. Recent studies have identified distinct structural elements within both the RNA and protein components of telomerase that modulate enzyme processivity. Pharmacological and genetic analysis suggest that telomerase processivity is a significant determinant of telomere length. Because telomere maintenance and the lack thereof have been linked to tumor progression and aging, further investigation of telomerase processivity may lead to novel medical intervention strategies.

摘要

端粒酶是一种细胞逆转录酶,负责大多数生物体中端粒的维持。它通过以整合的RNA组分作为模板,将端粒重复序列添加到预先存在的末端来实现这一点。与“典型的”逆转录酶相比,端粒酶的独特之处在于能够重复复制短的模板RNA片段,从而在单次结合事件后将多个重复拷贝添加到DNA底物上。这种独特的持续性特性暗示了该酶在其反应循环中必须精心编排的复杂构象变化。最近的研究已经在端粒酶的RNA和蛋白质组分中鉴定出不同的结构元件,这些元件调节酶的持续性。药理学和遗传学分析表明,端粒酶的持续性是端粒长度的重要决定因素。由于端粒维持及其缺失与肿瘤进展和衰老有关,对端粒酶持续性的进一步研究可能会带来新的医学干预策略。

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