XERODERMA-PIGMENTOSUM GROUP-F CAUSED BY A DEFECT IN A STRUCTURE-SPECIFIC DNA-REPAIR ENDONUCLEASE

Nucleotide excision repair, which is defective in xeroderma pigmentosu m (XP), involves incision of a DNA strand on each side of a lesion, We isolated a human gene homologous to yeast Rad1 and found that it corr ects the repair defects of XP group F as well as rodent groups 4 and 1 1. Causative mutations and strongly reduced levels of encoded protein were identified in XP-F patients. The XPF protein was purified from ma mmalian cells in a tight complex with ERCC1. This complex is a structu re-specific endonuclease responsible for the 5' incision during repair . These results demonstrate that the XPF, ERCC4, and ERCC11 genes are equivalent, complete the isolation of the XP genes that form the core nucleotide excision repair system, and solve the catalytic function of the XPF-containing complex.