走钢丝：R 环在基因组稳定性中的复杂平衡作用。
Walking a tightrope: The complex balancing act of R-loops in genome stability.
机构信息
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
出版信息
Mol Cell. 2022 Jun 16;82(12):2267-2297. doi: 10.1016/j.molcel.2022.04.014. Epub 2022 May 3.
Abstract
Although transcription is an essential cellular process, it is paradoxically also a well-recognized cause of genomic instability. R-loops, non-B DNA structures formed when nascent RNA hybridizes to DNA to displace the non-template strand as single-stranded DNA (ssDNA), are partially responsible for this instability. Yet, recent work has begun to elucidate regulatory roles for R-loops in maintaining the genome. In this review, we discuss the cellular contexts in which R-loops contribute to genomic instability, particularly during DNA replication and double-strand break (DSB) repair. We also summarize the evidence that R-loops participate as an intermediate during repair and may influence pathway choice to preserve genomic integrity. Finally, we discuss the immunogenic potential of R-loops and highlight their links to disease should they become pathogenic.
摘要
虽然转录是一个重要的细胞过程，但它也是基因组不稳定性的公认原因。当新生 RNA 与 DNA 杂交以取代非模板链作为单链 DNA（ssDNA）时，形成的非 B 型 DNA 结构 R 环部分导致了这种不稳定性。然而，最近的工作已经开始阐明 R 环在维持基因组方面的调节作用。在这篇综述中，我们讨论了 R 环导致基因组不稳定性的细胞环境，特别是在 DNA 复制和双链断裂（DSB）修复期间。我们还总结了 R 环作为修复过程中的中间产物参与的证据，并且可能影响路径选择以维持基因组完整性。最后，我们讨论了 R 环的免疫原性潜力，并强调了它们与疾病的联系，如果它们成为致病性的话。
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