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R-Loops 作为细胞调控因子和基因组威胁

R-Loops as Cellular Regulators and Genomic Threats.

机构信息

Department of Chemical and Systems Biology, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA 94305-5441, USA.

Department of Chemical and Systems Biology, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA 94305-5441, USA.

出版信息

Mol Cell. 2019 Feb 7;73(3):398-411. doi: 10.1016/j.molcel.2019.01.024.

Abstract

During transcription, the nascent RNA strand can base pair with its template DNA, displacing the non-template strand as ssDNA and forming a structure called an R-loop. R-loops are common across many domains of life and cause DNA damage in certain contexts. In this review, we summarize recent results implicating R-loops as important regulators of cellular processes such as transcription termination, gene regulation, and DNA repair. We also highlight recent work suggesting that R-loops can be problematic to cells as blocks to efficient transcription and replication that trigger the DNA damage response. Finally, we discuss how R-loops may contribute to cancer, neurodegeneration, and inflammatory diseases and compare the available next-generation sequencing-based approaches to map R-loops genome wide.

摘要

在转录过程中,新生的 RNA 链可以与模板 DNA 碱基配对,将非模板链置换为单链 DNA,并形成一种称为 R 环的结构。R 环在许多生命领域都很常见,并在某些情况下导致 DNA 损伤。在这篇综述中,我们总结了最近的研究结果,这些结果表明 R 环是转录终止、基因调控和 DNA 修复等细胞过程的重要调节剂。我们还强调了最近的工作表明,R 环可能对细胞造成问题,因为它们会阻碍有效的转录和复制,从而引发 DNA 损伤反应。最后,我们讨论了 R 环如何导致癌症、神经退行性疾病和炎症性疾病,并比较了现有的基于下一代测序的方法来绘制全基因组范围的 R 环。

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