Distinct roles of RECQL5 in RAD51-mediated fork reversal and transcription elongation

RECQL5 helicase has been implicated in the regulation of homologous recombination (HR), replication stress responses, transcription elongation, and resolution of transcription-replication conflicts. However, the underlying mechanism by which RECQL5 regulates multiple functions in genome maintenance is obscure. Here, we find that RECQL5 localizes to the stalled fork sites and restricts RAD51-mediated excessive fork reversal to promote unrestrained DNA synthesis. The replication defect in the absence of RECQL5 can be rescued by co-depletion of SMARCAL1/ZRANB3/HLTF/FBH1 fork remodelers and expression of HR-defective mutants of RAD51. The RAD51 regulation at the stalled fork sites by RECQL5 requires its binding to PCNA, RAD51, and helicase activity and is independent of its interaction with RNAPII. Notably, the RECQL5 mutant devoid of its interaction with RAD51 regulates transcription elongation comparable to that of wild-type RECQL5. Collectively, our data demonstrates that RECQL5 distinctly regulates transcription elongation and RAD51-mediated fork remodelling to safeguard the replicating genomes.