HUMAN XERODERMA-PIGMENTOSUM GROUP-G GENE ENCODES A DNA ENDONUCLEASE

Because of defective nucleotide excision repair of ultraviolet damaged DNA, xeroderma pigmentosum (XP) patients suffer from a high incidence of skin cancers. Cell fusion studies have identified seven XP complem entation groups, A to G. Previous studies have implicated the products of these seven XP genes in the recognition of ultraviolet-induced DNA damage and in incision of the damage-containing DNA strand. Here, we express the XPG-encoded protein in Sf9 insect cells and purify it to h omogeneity. We demonstrate that XPG is a single-strand specific DNA en donuclease, thus identifying the catalytic role of the protein in nucl eotide excision repair. We suggest that XPG nuclease acts on the singl e-stranded region created as a result of the combined action of the XP B helicase and XPD helicase at the DNA damage site.