Open AccessTargeted 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
Author(s) -
Bo Hang,
Singer B,
Geoffrey P. Margison,
Rhoderick H. Elder
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.24.12869
Subject(s) - dna glycosylase , hypoxanthine , dna , dna repair , microbiology and biotechnology , biochemistry , chemistry , dna damage , mutant , biology , enzyme , gene
It has previously been reported that 1,N 6 -ethenoadenine (ɛA), deaminated adenine (hypoxanthine, Hx), and 7,8-dihydro-8-oxoguanine (8-oxoG), but not 3,N 4 -ethenocytosine (ɛC), are released from DNAin 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 lesionsin 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 oligomers containing a single modified base was determined. The results showed that both testes and liver cells of these knockout mice completely lacked activity toward oligonucleotides containing ɛA and Hx, but retained wild-type levels of activity for ɛC and 8-oxoG. These findings indicate that (i ) the previously identified ɛA-DNA glycosylase and Hx-DNA glycosylase activities are functions of APNG; (ii ) the two structurally closely related mutagenic adducts ɛA and ɛC are repaired by separate gene products; and (iii ) APNG does not contribute detectably to the repair of 8-oxoG.