DNA damage-binding protein 1 (DDB1)

DNA damage-binding protein 1 (DDB1) is a highly conserved, large (127 kDa) protein that forms a core component of the CUL4-DDB1 E3 ubiquitin ligase complex and is essential for several DNA repair pathways, most notably nucleotide excision repair, where it forms a heterodimer with DDB2 to recognize UV-induced DNA lesions[1][2][4][7][8]. DDB1 serves as an adaptor or scaffold, bridging substrate receptors and the cullin core, thereby facilitating ubiquitination and turnover of numerous protein substrates involved in DNA repair, replication, chromatin remodeling, and cell cycle control[1][2][3][4]. Mutations in the DDB1 complex underlie the rare skin cancer syndrome xeroderma pigmentosum group E, and DDB1 is exploited by certain viruses (e.g., paramyxoviruses, HBV) to degrade host restriction factors[3][4]. While DDB1 has not been therapeutically targeted directly, its central role in maintaining genome stability makes it of high research and translational interest[2][4].

Other names

Damage-specific DNA binding protein 1DDBaXAP1XAP-1UV-DDB 1XPE-BFXPCeDDB p127 subunitDNA damage-binding protein aHBV X-associated protein 1UV-damaged DNA-binding factorUV-damaged DNA-binding protein 1XPE-binding factorXeroderma pigmentosum group E-complementing proteinDDBAUV-DDB1WHIKERSXPCEXPE127kDa

For drug discovery, potential mechanisms may include modulation of DNA repair or CUL4-DDB1 ubiquitin E3 ligase activity, but no clinical agents are established