RNA as a genome architect: G-loops in G-quadruplex regulation

Keywords G-quadruplex, RNA-DNA hybrids, Genome instability, DNA repair, Chromatin architecture For decades, DNA G-quadruplexes (G4s) have been recognized as non-canonical secondary structures enriched in regulatory genomic regions, influencing transcription, replication, and genome stability [1,2].While their formation is predictable, the mechanisms governing their dynamic resolution in vivo have remained elusive.The recent work by Sato et al. [3] provides a transformative answer, elucidating a complete RNA-driven regulatory cycle termed the "G-loop" pathway.The authors delineate a sophisticated process where a nascent RNA transcript invades the DNA duplex opposite a folded G4, forming a stable RNA-DNA hybrid structure (the G-loop), a process facilitated by heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and mediated by BReast-CAncer susceptibility gene 2 (BRCA2) and RAD51.Crucially, they uncover the disassembly mechanism: the dedicated helicases the DEAH-box helicase 36 (DHX36) and