Strand bias of UV-induced mutation at the adenine phosphoribosyltransferase locus in DNA repair-proficient versus-deficient CHO cells

Preferential repair of UV-induced photoproducts on the transcribed strand of actively transcribed genes should lead to a marked strand bias for UV-induced mutations. Most mammalian mutation studies to date have focused on a single gene locus (HPRT). We have been examining UV-induced photoproduct formation and repair at the CHO APRT locus. To determine whether UV-induced mutations at the APRT locus show a strand bias reflective of preferential repair of UV-photoproducts, we have examined the strand specificity of UV-induced APRT gene mutations in repair-proficient versus-deficient (ERCC1 mutant) cells. The majority of UV-induced mutations at the CHO APRT locus involve C→T transitions at dipyrimidine sites, with some transversions and tandem double mutations. Some strand bias for mutation was observed in repair-proficient cells; approximately twice as many UV-induced APRT gene mutations arose at dipyrimidine sites on the non-transcribed strand than on the transcribed strand. In repair-deficient cells, slightly more mutations occurred at dipyrimidine site on the transcribed strand. These results are consistent with preferential repair of UV-induced photoproducts on the transcribed strand, but the strand bias of mutation observed at the CHO APRT locus was much smaller than that which has been reported for the HPRT locus