Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N6-ethenoadenine and hypoxanthine but not of 3,N4-ethenocytosine or 8-oxoguanine.
Affiliation
Donner Laboratory, Lawrence Berkeley National Laboratory, University of California, 94720, USA.Issue Date
1997-11-25
Metadata
Show full item recordAbstract
It has previously been reported that 1,N6-ethenoadenine (epsilonA), deaminated adenine (hypoxanthine, Hx), and 7,8-dihydro-8-oxoguanine (8-oxoG), but not 3,N4-ethenocytosine (epsilonC), 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 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 epsilonA and Hx, but retained wild-type levels of activity for epsilonC and 8-oxoG. These findings indicate that (i) the previously identified epsilonA-DNA glycosylase and Hx-DNA glycosylase activities are functions of APNG; (ii) the two structurally closely related mutagenic adducts epsilonA and epsilonC are repaired by separate gene products; and (iii) APNG does not contribute detectably to the repair of 8-oxoG.Citation
Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N6-ethenoadenine and hypoxanthine but not of 3,N4-ethenocytosine or 8-oxoguanine. 1997, 94 (24):12869-74 Proc. Natl. Acad. Sci. U.S.A.Journal
Proceedings of the National Academy of Sciences of the United States of AmericaPubMed ID
9371767Type
ArticleLanguage
enISSN
0027-8424Collections
Related articles
- The type of DNA glycosylase determines the base excision repair pathway in mammalian cells.
- Authors: Fortini P, Parlanti E, Sidorkina OM, Laval J, Dogliotti E
- Issue date: 1999 May 21
- Alkylpurine-DNA-N-glycosylase excision of 7-(hydroxymethyl)-1,N6-ethenoadenine, a glycidaldehyde-derived DNA adduct.
- Authors: Wang P, Guliaev AB, Elder RH, Hang B
- Issue date: 2006 Jan 5
- Increased formation and persistence of 1,N(6)-ethenoadenine in DNA is not associated with higher susceptibility to carcinogenesis in alkylpurine-DNA-N-glycosylase knockout mice treated with vinyl carbamate.
- Authors: Barbin A, Wang R, O'Connor PJ, Elder RH
- Issue date: 2003 Nov 15
- A 55-kDa protein isolated from human cells shows DNA glycosylase activity toward 3,N4-ethenocytosine and the G/T mismatch.
- Authors: Hang B, Medina M, Fraenkel-Conrat H, Singer B
- Issue date: 1998 Nov 10
- Substrate specificity of human methylpurine DNA N-glycosylase.
- Authors: Asaeda A, Ide H, Asagoshi K, Matsuyama S, Tano K, Murakami A, Takamori Y, Kubo K
- Issue date: 2000 Feb 29