The stratum corneum and DNA repair do not completely protect keratinocytes from ultraviolet B. A third defense prevents cells with DNA photoproducts from becoming precancerous mutant cells: apoptosis of ultraviolet-damaged keratinocytes ("sunburn cells"). As signals for ultraviolet-induced apoptosis, some studies implicate DNA photoproducts in actively transcribed genes; other studies implicate non-nuclear signals. We traced and quantitated the in vivo DNA signal through several steps in the apoptosis-signaling pathway in haired @entity19 . Homozygous inactivation of @entity24333 , @entity58361 , or @entity25971 nucleotide excision repair genes directed the accumulation of DNA photoproducts to specific genome regions. Repair-defective @entity24333 -/- @entity19 were 7-10-fold more sensitive to sunburn cell induction than wild-type @entity19 , indicating that 86-90% of the ultraviolet B signal for keratinocyte apoptosis involved repairable photoproducts in DNA; the remainder involves unrepaired DNA lesions or nongenomic targets. @entity58361 -/- @entity19 , defective only in excising photoproducts from actively transcribed genes, were as sensitive as @entity24333 -/-, indicating that virtually all of the DNA signal originates from photoproducts in active genes. Conversely, @entity25971 -/- @entity19 , defective in repairing the untranscribed majority of the genome, were as resistant to apoptosis as wild type. Sunburn cell formation requires the @entity186 @entity5 suppressor protein; 90-96% of the signal for its induction in vivo involved transcribed genes. @entity1231 , which regulates the stability of @entity186 through degradation, was induced in vivo by low ultraviolet B doses but was suppressed at erythemal doses. DNA photoproducts in actively transcribed genes were involved in approximately 89% of the @entity1231 response.

The DNA damage signal for XXXX regulation, @entity186 induction, and sunburn cell formation in vivo originates from actively transcribed genes.

@entity19 :: ('10090', 'Species') :: ['mice'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity1231 :: ('17246(Tax:10090)', 'Gene') :: ['Mdm2'] @entity24333 :: ('22590(Tax:10090)', 'Gene') :: ['Xpa'] @entity186 :: ('22059(Tax:10090)', 'Gene') :: ['Trp53'] @entity25971 :: ('22591(Tax:10090)', 'Gene') :: ['Xpc'] @entity58361 :: ('319955(Tax:10090)', 'Gene') :: ['Csb']
@entity1231 :: (17246(Tax:10090),Gene) :: ['Mdm2']
