近日，荷兰莱顿大学
该课题组研究人员报告说，RNA转录本通过协调的G环组装和拆卸来控制G4景观。G-loop组装包括ATM和ATR激酶的激活，随后由BRCA2和RAD51介导的同源性定向入侵G4链对面的RNA。G环的拆卸通过DHX36-FANCJ介导的G4解绕来分解G4结构，从而触发溶核切口和随后DNA合成的杂交链更新。抑制G环拆卸会导致全球G4和R环积累，导致转录组失调、复制应激和基因组不稳定。这些发现建立了一个复杂的G环组装-拆卸机制，控制G4景观，对细胞内稳态和生存至关重要。
据了解，G-四联体（G4s）是一种普遍存在的DNA结构，它调节转录，但也威胁基因组的稳定性。如何控制G4的动态仍然知之甚少。
附：英文原文
Title: RNA transcripts regulate G-quadruplex landscapes through G-loop formation
Author: Koichi Sato, Jing Lyu, Jeroen van den Berg, Diana Braat, Victoria M. Cruz, Carmen Navarro Luzón, Joost Schimmel, Clara Esteban-Jurado, Malys Alemany, Jan Dreyer, Aiko Hendrikx, Francesca Mattiroli, Alexander van Oudenaarden, Marcel Tijsterman, Simon J. Elssser, Puck Knipscheer
Issue&Volume: 2025-06-12
Abstract: G-quadruplexes (G4s) are prevalent DNA structures that regulate transcription but also threaten genome stability. How G4 dynamics are controlled remains poorly understood. Here, we report that RNA transcripts govern G4 landscapes through coordinated G-loop assembly and disassembly. G-loop assembly involves activation of the ATM and ATR kinases, followed by homology-directed invasion of RNA opposite the G4 strand mediated by BRCA2 and RAD51. Disassembly of the G-loop resolves the G4 structure through DHX36-FANCJ–mediated G4 unwinding, which triggers nucleolytic incision and subsequent hybrid strand renewal by DNA synthesis. Inhibition of G-loop disassembly causes global G4 and R-loop accumulation, leading to transcriptome dysregulation, replication stress, and genome instability. These findings establish an intricate G-loop assembly-disassembly mechanism that controls G4 landscapes and is essential for cellular homeostasis and survival.
DOI: adr0493
Source: https://www.science.org/doi/10.1126/science.adr0493