HUMAN XERODERMA-PIGMENTOSUM GROUP-D GENE ENCODES A DNA HELICASE

XERODERMA pigmentosum (XP), a genetically heterogeneous human disease, results from a defect in nucleotide excision repair of ultraviolet-da maged DNA. XP patients are extremely sensitive to sunlight and suffer from a high incidence of skin cancers. Cell fusion studies have identi fied seven XP complementation groups, A-G1-3. Group D is of particular interest as mutations in this gene can also cause Cockayne's syndrome and trichothiodystrophy4. The XPD gene was initially named ERCC2 (exc ision repair cross complementing) as it was cloned using human DNA to complement the ultraviolet sensitivity of a rodent cell line5. We have purified the XPD protein to near homogeneity and show that it possess es single-stranded DNA-dependent ATPase and DNA helicase activities. W e tested whether XPD can substitute for its yeast counterpart RAD3, wh ich is essential for excision repair and for cell viability6. Expressi on of the XPD gene in Saccharomyces cerevisiae can complement the leth ality defect of a mutation in the RAD3 gene6, suggesting that XPD is a n essential gene in humans.