RAD9-HUS1-RAD1 interacting nuclear orphan 1 (RHNO1)

RAD9-HUS1-RAD1 interacting nuclear orphan 1 (RHNO1) is a nuclear protein that plays a critical role in the DNA damage response (DDR) by serving as an adaptor that interacts with the heterotrimeric RAD9-HUS1-RAD1 (9-1-1) DNA clamp complex. RHNO1 promotes activation of the ATR-CHK1 checkpoint in response to replication stress and is necessary for efficient repair of double-strand DNA breaks via microhomology-mediated end joining (MMEJ) and homologous recombination (HR). It accumulates during mitosis, where it is phosphorylated by Polo-like kinase 1 (PLK1) and recruits polymerase theta (POLQ) for mitotic DNA repair. The N-terminal APSES DNA-binding domain of RHNO1 mediates its interaction with the 9-1-1 complex. Overexpression or dysregulation of RHNO1 is associated with enhanced survival and chemoresistance of cancer cells, and may represent a promising target for therapeutic intervention in tumors that depend on heightened DDR signaling.

Other names

RHNO1RAD9, HUS1, RAD1-interacting nuclear orphan protein 1C12orf32RHINOHKMT1188MGC13204

Drugs targeting the ATR-CHK1 pathway may indirectly impact RHNO1 function by disrupting checkpoint activation and DNA damage repair. There is interest in targeting the RHNO1-9-1-1 interaction to down-regulate the DNA damage checkpoint in cancer therapy.