A DNA Damage Response Screen Identifies RHINO, a 9-1-1 and TopBP1 Interacting Protein Required for ATR Signaling

The DNA damage response (DDR) is a protein kinase cascade that orchestrates DNA repair processes via transcriptional and post-translational mechanisms. Cell cycle arrest is a hallmark of the DDR. We performed a damage-induced cell cycle arrest screen and uncovered a critical role for Fanconi anemia (FA) and homologous recombination (HR) proteins in ATR signaling. HR was required to maintain prolonged cell cycle arrest and to prevent massive genomic instability. Over 100 high scoring DDR candidates were interrogated for their roles in the DDR. Three proteins, INTS7, CLOCK and a novel protein RHINO, are recruited to sites of DNA damage. RHINO independently binds the Rad9-Rad1-Hus1 complex (9-1-1) and TopBP1. RHINO is recruited to sites of DNA damage by the 9-1-1 complex and is necessary to promote Chk1 activation. We suggest that RHINO functions together with the 9-1-1 complex and TopBP1 to fully activate ATR.