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人类复制蛋白A可解开端粒G-四链体。

Human replication protein A unfolds telomeric G-quadruplexes.

作者信息

Salas Tonatiuh Romero, Petruseva Irina, Lavrik Olga, Bourdoncle Anne, Mergny Jean-Louis, Favre Alain, Saintomé Carole

机构信息

Institut Jacques Monod, CNRS-ParisVI-ParisVII-UMR 7592, 2 place Jussieu, 75251 Paris cedex 05, France.

出版信息

Nucleic Acids Res. 2006;34(17):4857-65. doi: 10.1093/nar/gkl564. Epub 2006 Sep 14.

DOI:10.1093/nar/gkl564
PMID:16973897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1635258/
Abstract

G-quadruplex structures inhibit telomerase activity and must be disrupted for telomere elongation during S phase. It has been suggested that the replication protein A (RPA) could unwind and maintain single-stranded DNA in a state amenable to the binding of telomeric components. We show here that under near-physiological in vitro conditions, human RPA is able to bind and unfold G-quadruplex structures formed from a 21mer human telomeric sequence. Analyses by native gel electrophoresis, cross-linking and fluorescence resonance energy transfer indicate the formation of both 1:1 and 2:1 complexes in which G-quadruplexes are unfolded. In addition, quadruplex opening by hRPA is much faster than observed with the complementary DNA, demonstrating that this protein efficiently unfolds G-quartets. A two-step mechanism accounting for the binding of hRPA to G-quadruplexes is proposed. These data point to the involvement of hRPA in regulation of telomere maintenance.

摘要

G-四链体结构可抑制端粒酶活性，在S期进行端粒延长时必须将其破坏。有人提出，复制蛋白A（RPA）可以解开并维持单链DNA处于适合端粒成分结合的状态。我们在此表明，在接近生理的体外条件下，人RPA能够结合并展开由21聚体人端粒序列形成的G-四链体结构。通过非变性凝胶电泳、交联和荧光共振能量转移分析表明，形成了1:1和2:1的复合物，其中G-四链体被展开。此外，hRPA使四链体打开的速度比互补DNA快得多，表明该蛋白能有效地展开G-四重体。提出了一种解释hRPA与G-四链体结合的两步机制。这些数据表明hRPA参与了端粒维持的调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbb/1636391/629b9ace0b40/gkl564f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbb/1636391/cf3d70060fd8/gkl564f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbb/1636391/d5fbfe3565ad/gkl564f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbb/1636391/629b9ace0b40/gkl564f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbb/1636391/184147ffd9e8/gkl564f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbb/1636391/5007acbd3432/gkl564f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbb/1636391/12548303c62a/gkl564f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbb/1636391/7887b7547bb3/gkl564f4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbb/1636391/629b9ace0b40/gkl564f8.jpg

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