Xeroderma pigmentosum type G (XPG) is a human genetic disease exhibiting extreme sensitivity to sunlight. The XPG protein, a member of the flap endonuclease 1 (FEN-1) structure-specific DNA repair endonuclease family, is an enzyme essential for DNA repair of the major kinds of solar ultraviolet (UV)-induced DNA damages. Human XPG nuclease 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 29-amino acid region of human XPG (residues 981-1009) contains the PCNA binding activity. A conserved arginine in XPG (Arg992) is crucial for its PCNA binding activity. Replication Protein A (RPA) binds specifically and directly to two excision repair proteins, the xeroderma pigmentosum damage-recognition protein XPA and the endonuclease XPG.
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