Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group C

XERODERMA pigmentosum (XP) is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight, and, in some cases, neurological abnormalities^1,2. XP cells are defective in DNA repair³, and complementation of this defect has been used to identify eight genetic groups (A-G and variant)⁴. We have developed a simple, highly efficient complementary DNA expression system for use in human cells ⁵. Here we use this system to isolate a cDNA clone that restores the ultraviolet sensitivity and unscheduled DNA synthesis of XP-C cells to normal levels. The XP-C complementing clone XPCC encodes a highly hydrophilic protein which is composed of a predicted 823 amino acids and shares limited homology with the product of the yeast DNA repair gene RAD4. The XPCC transcript is undetectable by northern blotting in most XP-C cell lines examined.