Walking a tightrope: The complex balancing act of R-loops in genome stability.
Walking a tightrope: The complex balancing act of R-loops in genome stability.
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DOI：
10.1016/j.molcel.2022.04.014
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发表时间：
2022-06-16
期刊：
影响因子：
16
通讯作者：
Cimprich, Karlene A.
中科院分区：
文献类型：
--
作者：
Brickner, Joshua R.;Garzon, Jada L.;Cimprich, Karlene A.
虽然转录是一个重要的细胞过程，但矛盾的是，它也是基因组不稳定性的公认原因。R环，当新生RNA与DNA杂交以取代非模板链作为ssDNA时形成的非B DNA结构，是造成这种不稳定性的部分原因。然而，最近的工作已经开始阐明R环在维持基因组中的调节作用。在这篇综述中，我们讨论了细胞环境中，R-环有助于基因组的不稳定性，特别是在DNA复制和双链断裂（DSB）修复。我们还总结了证据，R环参与修复过程中的中间体，并可能影响路径的选择，以保持基因组的完整性。最后，我们讨论了R环的免疫原性潜力，并强调它们与疾病的联系，如果它们成为致病性的。虽然R环是基因组不稳定性、复制应激和DNA损伤的公认来源，但人们越来越认识到它们如何有助于基因组的维持。在这里，Brickner et.导航这种二分法，并讨论R环失调的后果，强调与免疫反应和疾病进展的联系。
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 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. While R-loops are a well-recognized source of genomic instability, replication stress, and DNA damage, there is a growing appreciation for how they contribute to genome maintenance. Here, Brickner et. al. navigate this dichotomy and discuss the consequences of R-loop dysregulation, highlighting links to the immune response and disease progression.
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