DHX9-dependent recruitment of BRCA1 to RNA is required to promote DNA end resection in homologous recombination

DExD/H-box helicase 9 (DHX9/RNA helicaseA) is ubiquitously expressed ATP-dependent helicase that unwinds a variety of complex DNA and RNA secondary structures, suggesting it might have a role in DNA replication and the repair of DNA damage. Here we identify a pivotal role for DHX9 in homologous recombination (HR). Cells that are deficient in DHX9 are impaired in the generation of single stranded DNA (ssDNA) by DNA end resection. Consequently these cells fail to recruit RPA and RAD51 to sites of DNA damage and are hypersensitive to treatment with the DNA damaging agents camptothecin and Olaparib. A critical early step in the initiation of HR is the recruitment of BRCA1 mediator protein to DNA damage to promote DNA resection. We show here that recruitment of BRCA1 to DNA damage foci is dependent on its interaction with DHX9 to form the BRCA1-D complex, which binds to nascent RNA. Together our data identify a pivotal role for DHX9 in homologous recombination and highlight the important contribution of RNA in the recruitment of BRCA1 to DNA damage for the repair of DNA breaks