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.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95216
Title:
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.
Authors:
Hang, B; Singer, B; Margison, Geoffrey P; Elder, Rhoderick H
Abstract:
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.
Affiliation:
Donner Laboratory, Lawrence Berkeley National Laboratory, University of California, 94720, USA.
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 America
Issue Date:
25-Nov-1997
URI:
http://hdl.handle.net/10541/95216
PubMed ID:
9371767
Type:
Article
Language:
en
ISSN:
0027-8424
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHang, Ben
dc.contributor.authorSinger, Ben
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorElder, Rhoderick Hen
dc.date.accessioned2010-03-30T08:35:56Z-
dc.date.available2010-03-30T08:35:56Z-
dc.date.issued1997-11-25-
dc.identifier.citationTargeted 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.en
dc.identifier.issn0027-8424-
dc.identifier.pmid9371767-
dc.identifier.urihttp://hdl.handle.net/10541/95216-
dc.description.abstractIt 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.en
dc.language.isoenen
dc.subject.meshAdenine-
dc.subject.meshAnimals-
dc.subject.meshCell-Free System-
dc.subject.meshCytosine-
dc.subject.meshDNA Glycosylases-
dc.subject.meshDNA Repair-
dc.subject.meshGuanine-
dc.subject.meshHydrolysis-
dc.subject.meshHypoxanthine-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshMice, Knockout-
dc.subject.meshN-Glycosyl Hydrolases-
dc.subject.meshRecombinant Proteins-
dc.subject.meshSubstrate Specificity-
dc.titleTargeted 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.en
dc.typeArticleen
dc.contributor.departmentDonner Laboratory, Lawrence Berkeley National Laboratory, University of California, 94720, USA.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen
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