DNA-REPAIR AND ULTRAVIOLET MUTAGENESIS IN CELLS FROM A NEW PATIENT WITH XERODERMA-PIGMENTOSUM GROUP-G AND COCKAYNE-SYNDROME RESEMBLE XERODERMA-PIGMENTOSUM CELLS

Xeroderma pigmentosum (XP)/Cockayne syndrome (CS) complex is a combina tion of clinical features of two rare genetic disorders in one individ ual, A sun-sensitive boy (XP20BE) who had severe symptoms of CS, with dwarfism, microcephaly, retinal degeneration, and mental impairment, h ad XP-type pigmentation and died at 6 y with marked cachexia (weight 1 4.5 lb) without skin cancers, We evaluated his cultured cells for char acteristic CS or XP DNA-repair abnormalities. The level of ultraviolet (UV)-induced unscheduled DNA synthesis was less than 5% of normal, ch aracteristic of the excision-repair defect of XP. Cell fusion studies indicated that his cells were in XP complementation group G, His cells were hypersensitive to killing by UV, and their post-UV recovery of R NA synthesis was abnormally low, features of both CS and XP, Post-UV s urvival of plasmid pSP189 in his cells was markedly reduced, and post- UV plasmid mutation frequency was higher than with normal cells, as in both CS and XP, Sequence analysis of the mutated plasmid marker gene showed normal frequency of plasmids with multiple base substitutions, as in CS, and an abnormally increased frequency of G:C --> A:T mutatio ns, a feature of XP. Transfection of UV-treated pRSV cat with or witho ut photoreactivation revealed that his cells, like XP cells, could not repair either cyclobutane pyrimidine dimers or non-dimer photoproduct s. These results indicate that the DNA-repair features of the XP20BE ( XP-G/CS) cells are phenotypically more like XP cells than CS cells, wh ereas clinically the CS phenotype is more prominent than XP.