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人端粒保护蛋白1(POT1)在体外是端粒酶活性的负调节因子。

Human protection of telomeres 1 (POT1) is a negative regulator of telomerase activity in vitro.

作者信息

Kelleher Colleen, Kurth Isabel, Lingner Joachim

机构信息

ISREC, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.

出版信息

Mol Cell Biol. 2005 Jan;25(2):808-18. doi: 10.1128/MCB.25.2.808-818.2005.

Abstract

The telomeric single-strand DNA binding protein protection of telomeres 1 (POT1) protects telomeres from rapid degradation in Schizosaccharomyces pombe and has been implicated in positive and negative telomere length regulation in humans. Human POT1 appears to interact with telomeres both through direct binding to the 3' overhanging G-strand DNA and through interaction with the TRF1 duplex telomere DNA binding complex. The influence of POT1 on telomerase activity has not been studied at the molecular level. We show here that POT1 negatively effects telomerase activity in vitro. We find that the DNA binding activity of POT1 is required for telomerase inhibition. Furthermore, POT1 is incapable of inhibiting telomeric repeat addition to substrate primers that are defective for POT1 binding, suggesting that in vivo, POT1 likely affects substrate access to telomerase.

摘要

端粒单链DNA结合蛋白端粒保护蛋白1(POT1)可保护裂殖酵母中的端粒免于快速降解,并且在人类端粒长度的正负调控中发挥作用。人POT1似乎通过直接结合3'悬垂的G链DNA以及与TRF1双链体端粒DNA结合复合物相互作用来与端粒相互作用。尚未在分子水平上研究POT1对端粒酶活性的影响。我们在此表明,POT1在体外对端粒酶活性具有负面影响。我们发现POT1的DNA结合活性是抑制端粒酶所必需的。此外,POT1无法抑制向对POT1结合有缺陷的底物引物添加端粒重复序列,这表明在体内,POT1可能会影响底物与端粒酶的结合。

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