DHX30 is a replication stress-responsive R-loop helicase that safeguards genome stability

DHX30 is a replication stress-responsive R-loop helicase that safeguards genome stability by resolving R-loops, with nuclear abundance increasing after aphidicolin or camptothecin treatment.

• Why it matters: R-loops formed during transcription can block replication forks and cause replication stress and genome instability, but how specific helicases protect genome integrity is not fully understood.
• What they did: The study identified DHX30 as a DExH-box RNA helicase and tested its localization, stress-induced nuclear abundance, and function in human cells and zebrafish, alongside biochemical unwinding of R-loop substrates with a 3' RNA overhang.
• The result: DHX30 deficiency caused RNA:DNA hybrid accumulation, R-loop-dependent DNA double-strand breaks, micronuclei, reduced DNA synthesis, and altered immediate-early stress gene expression, supporting DHX30 as a conserved R-loop-resolving helicase.