hRAD30 mutations in the variant form of xeroderma pigmentosum

Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by a high incidence of skin cancers. Yeast RAD30 encodes a DNA polymerase i nvolved in the error-free bypass of ultraviolet (UV) damage. Here it is sho wn that XP variant (XP-V) cell lines harbor nonsense or frameshift mutation s in hRAD30, the human counterpart of yeast RAD30. Of the eight mutations i dentified, seven would result in a severely truncated hRad30 protein. These results indicate that defects in hRAD30 cause XP-V, and they suggest that error-free replication of UV lesions by hRad30 plays an important role in m inimizing the incidence of sunlight-induced skin cancers.