Ultraviolet-indu ced mutations inCockayne syndrome cells are primarily caused bycyclobutane dimerphotoproducts while repair ofother photoproducts isnormal (DNArepair/xeroderma pigmentosum/skin cancer/shuttle vector/photoreactivation)

We compared thecontribution tomutagene- sisinCockayne syndrome (CS)cells ofthemajor class ofUV photoproducts, thecyclobutane pyrimidine dimer, tothatof other DNA photoproducts byusing themutagenesis shuttle vector pZ189. Lymphoblastoid cell lines fromtheDNArepair- deficient disorders CSandxeroderma pigmentosum (XP)and anormal line weretransfected withUV-treated pZ189. Cy- clobutane dimers wereselectively removed before transfection byphotoreactivation (PR), leaving nondimer photoproducts intact. After UVexposure andreplication inCSandXPcells, plasmid survival wasabnormally reduced andmutation fre- quency wasabnormally elevated. After PR,plasmid survival increased andmutation frequency inCScells decreased to normal levels butremained abnormal inXPcells. Sequence analysis of>200mutantplasmids showed that withCScells a major mutational hotspotwascaused byunrepaired cyclo- butane dimers. These dataindicate that withbothCSandXP cyclobutane dimers aremajorphotoproducts generating re- ducedplasmid survival andincreased mutation frequency. However, unlike XP,CS cells areproficient inrepair of nondimer photoproducts. Since XPbutnotCSpatients havea highfrequency ofUV-induced skincancers, ourdatasuggest that prevention ofUV-induced skin cancers isassociated with proficient repair ofnondimer photoproducts.