STRAND-SPECIFIC REMOVAL OF CYCLOBUTANE PYRIMIDINE DIMERS FROM THE P53GENE IN THE EPIDERMIS OF UVB-IRRADIATED HAIRLESS MICE

Removal of UVB-induced cyclobutane pyrimidine dimers (CPD) from each o f the two strands of the transcriptionally active p53 tumor suppressor gene and the hypoxanthine-guanine phosphoribosyltransferase (HPRT) ge ne was determined in the epidermis of the hairless mouse using the CPD -specific enzyme T4 endonuclease V. Mice were exposed to a single dose of UVB (2 kJ/m(2)) and kept in darkness for up to 24 h. About 80% of the CPD were removed from the transcribed strand of the p53 and HPRT g enes within 24 h. Most rapid removal was observed during the first 4 h . Tn contrast, very little removal of CPD from the nontranscribed stra nd of the p53 and the HPRT genes was observed in 24 h. The same low le vel of repair was observed in the inactive cmos proto-oncogene. The ef ficient repair of the transcribed strand compared to the nontranscribe d strand of transcriptionally active genes in the epidermis of the hai rless mouse resembles the repair of CPD in cultured rodent cells. More over, the selective removal of CPD from the transcribed strand of the p53 gene correlates well with the known strand bias of u.v.-induced mu tations at dipyrimidine sites in the p53 gene of u.v.- induced mouse s kin tumors.