RAD18 transmits DNA damage signaling to elicit homologous recombination repair

To maintain genome stability, cells respond to DNA damage by activating signaling pathways that govern cell cycle checkpoints and initiate DNA repair. Cell cycle checkpoint controls should somehow connect with DNA repair processes, however, exactly how such coordination occurs in vivo is largely unknown. Here we revealed a novel role of RAD18 as the integral component that translates the damage response signal to orchestrate homologous recombination (HR) repair. We show that RAD18 promotes HR in a manner strictly dependent upon its ability to be recruited to the sites of DNA breaks and this recruitment relies on a well-defined DNA damage-signaling pathway mediated by another E3 ligase RNF8. We further demonstrate that RAD18 functions as an adaptor to facilitate HR via a direct interaction with RAD51C. Together, our data uncovers RAD18 as a key factor that orchestrates HR repair via surveillance of the DNA damage signal.