R-loop structures are a prevalent class of alternative non-B DNA structures that form during transcription upon invasion of the DNA template by the nascent RNA. R-loops form universally in the genomes of organisms ranging from bacteriophages, bacteria and yeasts to plants and animals, including mammals. A growing body of work has linked these structures to both physiological and pathological processes, in particular to genome instability. The rising interest in R-loops is placing new emphasis on understanding the fundamental physicochemical forces driving their formation and stability. Pioneering work in Escherichia coli revealed that DNA topology, in particular negative DNA superhelicity, plays a key role in driving R-loops. A clear role for DNA sequence was later uncovered. Here, we review and synthesize available evidence on the roles of DNA sequence and DNA topology in controlling R-loop formation and stability. Factoring in recent developments in R-loop modeling and single-molecule profiling, we propose a coherent model accounting for the interplay between DNA sequence and DNA topology in driving R-loop structure formation. This model reveals R-loops in a new light as powerful and reversible topological stress relievers, an insight that significantly expands the repertoire of R-loops' potential biological roles under both normal and aberrant conditions.

中文翻译：

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R环结构在拓扑应力管理中的新兴作用。

R-环结构是一类常见的替代性非B DNA结构，其在新生RNA入侵DNA模板后的转录过程中形成。R环普遍存在于生物基因组中，从噬菌体，细菌和酵母菌到动植物，包括哺乳动物。越来越多的工作将这些结构与生理和病理过程联系在一起，特别是与基因组不稳定性联系在一起。人们对R环的兴趣不断提高，将新的重点放在了理解驱动其形成和稳定性的基本物理化学力上。大肠杆菌的开拓性工作表明，DNA拓扑结构，特别是负DNA超螺旋性，在驱动R环中起关键作用。后来发现了DNA序列的明确作用。这里，我们审查和综合有关DNA序列和DNA拓扑在控制R环形成和稳定性中的作用的现有证据。考虑到R环建模和单分子分析的最新发展，我们提出了一个相干模型，该模型考虑了驱动R环结构形成的DNA序列和DNA拓扑之间的相互作用。该模型以新的方式揭示了R环，它们是功能强大且可逆的拓扑应力释放器，这一见解极大地扩展了R环在正常和异常条件下的潜在生物学作用范围。我们提出了一个协调的模型，该模型考虑了驱动R环结构形成的DNA序列与DNA拓扑之间的相互作用。该模型以新的方式揭示了R环，它们是功能强大且可逆的拓扑应力释放器，这一见解极大地扩展了R环在正常和异常条件下的潜在生物学作用范围。我们提出了一个协调的模型，该模型考虑了驱动R环结构形成的DNA序列与DNA拓扑之间的相互作用。该模型以新的方式揭示了R环，它们是功能强大且可逆的拓扑应力释放器，这一见解极大地扩展了R环在正常和异常条件下的潜在生物学作用范围。