Xeroderma pigmentosum (XP) is characterized high sensitivity to UV light and high incidence of skin cancer. XP fall into seven complementation groups, XPA to XPG. They are lacking a functional helicase, endonuclease, or lesion-recognizing proteins involved base excision repair. Xeroderma pigmentosum type G (XPG) is one of the rarest and phenotypically heterogeneous forms of genetic disorder. XPG gene encodes an acidic protein with an estimated MW ~133kD that confers normal UV-resistance. XPG is a member of the flap endonuclease 1 (FEN-1) structure-specific DNA repair endonuclease family responsible to UV-induced DNA repair. Human XPG makes the 3' incision during nucleotide excision repair of DNA. The enzyme cleaves model DNA bubble structures specifically near the junction of unpaired DNA with a duplex region. A 29aa region of human XPG (981-1009aa) contains the PCNA binding activity. A conserved Arg in XPG (Arg992) is crucial for its PCNA-binding activity. Replication protein A (RPA) binds specifically and directly to two excision repair proteins, Xeroderma pigmentosum damage recognition protein XPA and the endonuclease XPG.