Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N~6-ethenoadenine and hypoxanthine but not of 3,N~4-ethenocytosine or 8-oxoguanine

摘要

It has previously been reported that 1,N~6- ethenoadenine (εA), deaminated adenine (hypoxanthine, Hx), and 7,8-dihydro-8-oxoguanine (8-oxoG), but not 3,N~4- ethenocytosine (εC), are released from DNA in vitro by the DNA repair enzyme alkylpurine-DNA-N-glycosylase (APNG). To assess the potential contribution of APNG to the repair of each of these mutagenic lesions in vivo, we have used cell-free extracts of tissues from APNG-null mutant mice and wild-type controls. The ability of these extracts to cleave defined oli- gomers containing a single modified base was determined. The results showed that both testes and liver cells of these knock- out mice completely lacked activity toward oligonucleotides containing εA and Hx, but retained wild-type levels of activity for C and 8-oxoG.