X-ray repair cross-complementing protein 5 (XRCC5)

X-ray repair cross-complementing protein 5 (XRCC5), commonly called Ku80, is a core component of the non-homologous end joining (NHEJ) DNA double-strand break repair machinery. It forms a heterodimer with Ku70 (XRCC6) to create the Ku complex, which binds to DNA double-strand break ends, initiates recruitment of other repair factors, and is crucial for maintaining genome stability. XRCC5's functions include DNA end binding, assembly of the DNA-dependent protein kinase (DNA-PK) complex, and end-processing activities required for effective repair and V(D)J recombination in immune cells. XRCC5/Ku80 also plays roles in transcriptional regulation, ribosomal RNA processing, and innate immune response. Deregulation or mutation in XRCC5 is associated with increased cancer risk, immunodeficiency, radiosensitivity, and autoimmune phenomena[1][2][3][4][5][6][7].

Other names

Ku80Ku86KARP-1KARP1KUB2CTC85CTCBFTLAAG22P2NFIVThyroid-lupus autoantigenLupus Ku autoantigen protein p86Nuclear factor IVDNA repair protein XRCC586 kDa subunit of Ku antigenATP-dependent DNA helicase 2 subunit 2ATP-dependent DNA helicase II 80 kDa subunitCTC box-binding factor 85 kDa subunitKu autoantigen, 80kDa

Drug candidates working at this target generally act by inhibiting DNA-dependent protein kinase (DNA-PK) activity, leading to impaired NHEJ DNA repair and sensitization to DNA-damaging agents (e.g., ionizing radiation, chemotherapy)