Cell cycle checkpoint protein RAD17 (RAD17)

Cell cycle checkpoint protein RAD17 (RAD17) is a key component of the checkpoint clamp loader complex that senses DNA damage and replication stress[1][2][3]. By recognizing structures such as RPA-coated single-stranded DNA at stalled replication forks, RAD17 recruits the heterotrimeric 9–1–1 clamp complex (Rad9–Rad1–Hus1), which subsequently activates ATR-mediated checkpoint signaling to delay the cell cycle and preserve genomic integrity[1][2]. RAD17 is closely related to the replication factor C (RFC) subunits—unlike canonical RFC, RAD17 replaces the large RFC1 subunit in an alternative clamp loader complex that loads the 9–1–1 complex at DNA damage sites, specifically at 5′-recessed DNA junctions[2][3]. Post-translational modifications, notably phosphorylation by ATR and ATM kinases, are essential for its interaction with checkpoint mediators and for the regulation of its localization and function[1][3]. While not a direct therapeutic drug target at present, RAD17 is essential in the DNA damage response and is implicated in cancer and other genomic instability syndromes. Its phosphorylated form may serve as a biomarker for checkpoint activation[3].

Other names

RAD17R24LhRad17Rad24RAD17SpCCYCRF-C/activator 1 homologHRAD17RAD17SPRAD24Rad17-like proteincell cycle checkpoint protein RAD17RAD1 homologRAD17 homologRF-C activator 1 homolog

Not targeted by approved drugs; theoretical mechanisms might include inhibition or modulation of the checkpoint clamp loader–mediated ATR/CHK1 signaling pathway