Replication protein A plays multifaceted roles complementary to specialized helicases in processing G-quadruplex DNA.
Replication protein A plays multifaceted roles complementary to specialized helicases in processing G-quadruplex DNA.
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复制蛋白 A 在处理 G-四链体 DNA 过程中发挥与特殊解旋酶互补的多方面作用
DOI：
10.1016/j.isci.2021.102493
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发表时间：
2021-05-21
期刊：
影响因子：
5.8
通讯作者：
Hou XM
中科院分区：
文献类型：
--
作者：
Wang YR;Guo TT;Zheng YT;Lai CW;Sun B;Xi XG;Hou XM
G-四链体 (G4) 是非常规 DNA 结构，在 DNA 代谢中发挥着关键作用。为了解决那些可能导致复制叉停滞和基因组不稳定的结构，需要单链 DNA 结合蛋白和解旋酶。在这里，我们使用单分子 FRET 描述了 G4 上 RPA 和解旋酶之间的相互作用。我们首先发现人类 RPA 通过在 ssDNA 折叠前抢占其位置来有效阻止 G4 的形成。 RPA 与折叠的 G4 的相互作用也存在差异。然而，人类 BLM 和酵母 Pif1 等解旋酶与 RPA 具有不同的 G4 偏好，主要基于环长度。更重要的是，RPA 和这些解旋酶都是 G4 稳定解折叠所必需的，因为 RPA 促进解旋酶介导的重复解折叠进入持续线性状态。此外，BLM 可以穿越 RPA 暂时中断的 G4 障碍，并继续展开下游双工。我们最终提出了RPA在预防、解决和协助解旋酶消除G4方面的上述功能的潜在机制。 RPA 通过在折叠前抢占 ssDNA 来有效阻止 G4 形成 环长度可以通过 RPA 和解旋酶将折叠的 G4 引导至不同的解折叠方式 RPA 促进解旋酶介导的重复 G4 解折叠成持续线性状态 RPA 协助 BLM 克服 G4 障碍并继续解旋下游双链分子结构；分子生物学
G-quadruplexes (G4s) are non-canonical DNA structures with critical roles in DNA metabolisms. To resolve those structures that can cause replication fork stalling and genomic instability, single-stranded DNA-binding proteins and helicases are required. Here, we characterized the interplay between RPA and helicases on G4s using single-molecule FRET. We first discovered that human RPA efficiently prevents G4 formation by preempting ssDNA before its folding. RPA also differentially interacts with the folded G4s. However, helicases such as human BLM and yeast Pif1 have different G4 preferences from RPA mainly based on loop lengths. More importantly, both RPA and these helicases are required for the stable G4 unfolding, as RPA promotes helicase-mediated repetitive unfolding into durative linear state. Furthermore, BLM can traverse G4 obstacles temporarily disrupted by RPA and continue to unwind downstream duplex. We finally proposed the mechanisms underlying above functions of RPA in preventing, resolving, and assisting helicases to eliminate G4s. RPA efficiently prevents G4 formation by preempting ssDNA before its folding Loop length may direct folded G4s to different unfolding way by RPA and helicases RPA promotes helicase-mediated repetitive G4 unfolding into durative linear state RPA assists BLM to overcome G4 obstacle and continue to unwind downstream duplex Molecular structure; Molecular biology
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DOI：
10.1038/nrg3296
发表时间：
2012-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
21.8
作者：
Di Antonio M;Ponjavic A;Radzevičius A;Ranasinghe RT;Catalano M;Zhang X;Shen J;Needham LM;Lee SF;Klenerman D;Balasubramanian S
通讯作者：
Balasubramanian S
影响因子：
46.9
作者：
Chambers, Vicki S.;Marsico, Giovanni;Balasubramanian, Shankar
通讯作者：
Balasubramanian, Shankar
影响因子：
64.8
作者：
Chen MC;Tippana R;Demeshkina NA;Murat P;Balasubramanian S;Myong S;Ferré-D'Amaré AR
通讯作者：
Ferré-D'Amaré AR
影响因子：
6.4
作者：
Maestroni, Laetitia;Audry, Julien;Corda, Yves
通讯作者：
Corda, Yves