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重组端粒酶进行连续核苷酸和重复添加的易位事件的改进模型。

A modified model for translocation events of processive nucleotide and repeat additions by the recombinant telomerase.

机构信息

Institute of Physics, Chinese Academy of Sciences, Beijing, China.

出版信息

Biophys Chem. 2010 Dec;153(1):83-96. doi: 10.1016/j.bpc.2010.10.007. Epub 2010 Oct 16.

Abstract

Telomerase is a unique reverse transcriptase that extends the single-stranded 3' overhangs of telomeres by copying a short template sequence within the integral RNA component of the enzyme. It shows processive nucleotide and repeat addition activities, which are realized via two types of movements: translocation of the DNA:RNA hybrid away from the active site following each nucleotide addition and translocation of the 3' end of the DNA primer relative to the RNA template after each round of repeat synthesis. Here, a model is presented to describe these two types of translocation events by the recombinant Tetrahymena telomerase, via the modification of the model that has been proposed recently. Using the present model, the dynamics of the dissociation of the DNA primer from the telomerase and the dynamics of the disruption of the DNA:RNA hybrid and then repositioning of the product 3' end to the beginning of the template are studied quantitatively. Their effects on the repeat addition processivity are theoretically studied. The theoretical results are in agreement with the available experimental data.

摘要

端粒酶是一种独特的逆转录酶,通过复制酶的完整 RNA 成分内的短模板序列来延伸端粒的单链 3'突出端。它显示出连续的核苷酸和重复添加活性,这是通过两种类型的运动实现的:在每个核苷酸添加后,DNA:RNA 杂种从活性位点的易位和在每一轮重复合成后,相对于 RNA 模板,DNA 引物的 3'末端的易位。在此,通过最近提出的模型的修改,提出了一个模型来描述通过重组 Tetrahymena 端粒酶的这两种类型的易位事件。使用当前的模型,定量研究了 DNA 引物与端粒酶解离的动力学以及 DNA:RNA 杂种的破坏和然后将产物 3'末端重新定位到模板起始处的动力学。理论上研究了它们对重复添加过程的影响。理论结果与现有实验数据一致。

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