DNA helicase that plays an important role in DNA replication, transcription and repair (PubMed:20643585, PubMed:22973052). Binds to the RNA polymerase II subunit POLR2A during transcription elongation and suppresses transcription-associated genomic instability (PubMed:20231364). Associates also with POLR1A and enforces the stability of ribosomal DNA arrays (PubMed:27502483). Plays an important role in mitotic chromosome separation after cross-over events and cell cycle progress (PubMed:22013166). Mechanistically, removes RAD51 filaments protecting stalled replication forks at common fragile sites and stimulates MUS81-EME1 endonuclease leading to mitotic DNA synthesis (PubMed:28575661). Required for efficient DNA repair, including repair of inter-strand cross-links (PubMed:23715498). Stimulates DNA decatenation mediated by TOP2A. Prevents sister chromatid exchange and homologous recombination. ATP + H2O = ADP + H(+) + phosphate Monomer. Interacts with TOP2A, TOP3A and TOP3B (PubMed:20231364, PubMed:10710432). Isoform beta interacts with RNA polymerase II subunit POLR2A (PubMed:20348101, PubMed:20231364, PubMed:23748380). Identified in a complex with the RNA polymerase II core bound to DNA (PubMed:20348101, PubMed:20231364). Interacts (via C-terminus) with POLR1A (PubMed:27502483). Isoform beta interacts with RAD51 (PubMed:20348101, PubMed:20231364). Interacts with WRN; this interaction stimulates WRN helicase activity on DNA fork duplexes (PubMed:23180761). Interacts with MUS1; this interaction promotes MUS81-dependent mitotic DNA synthesis (PubMed:28575661). Recruited to sites of DNA damage, such as single-strand breaks and inter-strand cross-links, and at stalled replication forks. Re-localizes from the nucleolus into the nucleus after replicative stress and significantly associates with WRN during S-phase (PubMed:23180761). Ubiquitous. Phosphorylated by CDK1 at Ser-727; this phosphorylation is required for RECQL5-mediated disruption of RAD51 filaments on stalled replication forks. Belongs to the helicase family. RecQ subfamily.