The age‐related decline of helicase function—how G‐quadruplex structures promote genome instability

Abstract

The intricate mechanisms underlying transcription‐dependent genome instability involve G‐quadruplexes (G4) and R‐loops. This perspective elucidates the potential link between these structures and genome instability in aging. The co‐occurrence of G4 DNA and RNA–DNA hybrid structures (G‐loop) underscores a complex interplay in genome regulation and instability. Here, we hypothesize that the age‐related decline of sirtuin function leads to an increase in acetylated helicases that bind to G4 DNA and RNA–DNA hybrid structures, but are less efficient in resolving them. We propose that acetylated, less active, helicases induce persistent G‐loop structures, promoting transcription‐dependent genome instability in aging.