ERCC excision repair 4, endonuclease catalytic subunit (ERCC4)

ERCC excision repair 4, endonuclease catalytic subunit (ERCC4, commonly called XPF), is a structure-specific DNA repair enzyme that functions as the catalytic component of the ERCC1–XPF endonuclease complex[1][4][5]. This complex is essential in the nucleotide excision repair (NER) pathway, where it cleaves the 5′ side of DNA adjacent to helix-distorting lesions caused by ultraviolet light or various chemotherapeutic agents. ERCC4–XPF also participates in the repair of DNA interstrand crosslinks, some forms of double-strand break repair by homologous recombination, and in the maintenance of telomere length. Mutations or deficiencies in ERCC4 cause a range of rare, recessive inherited human disorders including xeroderma pigmentosum (XP-F), Cockayne syndrome, Fanconi anemia (FANCQ), and progeroid syndromes, leading to heightened cancer susceptibility, premature aging, and developmental abnormalities. In oncology, reduced activity of ERCC4–XPF sensitizes cells to DNA-damaging agents, making it an emerging target for cancer sensitization therapies, although no drugs specifically approved for ERCC4 modulation are currently available[1][5].

Other names

DNA repair endonuclease XPFXPFERCC11RAD1FANCQDNA excision repair protein ERCC-4Xeroderma pigmentosum group F-complementing proteinexcision repair cross-complementation group 4XFEPS

Proposed mechanism for experimental inhibitors: Direct inhibition of ERCC1–XPF complex nuclease activity, aiming to prevent DNA repair in cancer cells, thereby increasing their sensitivity to chemotherapeutic agents causing DNA damage[1].