Identical defects in DNA repair in xeroderma pigmentosum group G and rodent ERCC group 5

Humans with the complementation group G form of the inherited syndrome xeroderma pigmentosum (XP) are hypersensitive to solar ultraviolet light because of a defect in nucleotide-excision repair of DNA. Some individuals are also affected with Cockayne's syndrome, and have neurological abnormalities. Here we report that the DNA repair deficiency of XP-G cell extracts can be corrected by addition of protein fractions from normal cells. Repair proficiency can also be restored by mixing XP-G cell extracts with extracts from different repair-defective cell lines, with one exception. Extracts from cells representing group 5 of a set of ultraviolet-sensitive rodent mutants fail to complement XP-G extracts. XP-G and group 5 correcting activities co-elute after approximately 1,000-fold purification from HeLa cells. An antibody directed against a recombinant fragment of the XP-G complementing protein (XPGC) inhibits excision repair by normal cell extracts, and activity can be restored with an XP-G/group 5 complementing fraction. These data strongly suggest that the XPGC and group 5 correcting (ERCC5) proteins are identical.