Repair and replication of plasmids with site-specific 8-oxodG and 8-AAFdG residues in normal and repair-deficient human cells
| العنوان: | Repair and replication of plasmids with site-specific 8-oxodG and 8-AAFdG residues in normal and repair-deficient human cells |
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| المؤلفون: | H. C. P. F. Roelen, A.J.M. Berns, J. C. Klein, C.P. Saris, M.J. Bleeker, J.G. Westra, H. F. Brugghe, J. H. Van Boom, H. Van Den Elst, E. Kriek, G. A. Van Der Marel |
| المصدر: | Nucleic Acids Research. 20:4437-4443 |
| بيانات النشر: | Oxford University Press (OUP), 1992. |
| سنة النشر: | 1992 |
| مصطلحات موضوعية: | DNA Replication, DNA Repair, DNA repair, DNA polymerase, Molecular Sequence Data, medicine.disease_cause, chemistry.chemical_compound, Plasmid, Genetics, medicine, Humans, Mutation, Base Sequence, biology, Mutagenicity Tests, Mutagenesis, DNA replication, Deoxyguanine Nucleotides, Deoxyguanosine, Molecular biology, Oligodeoxyribonucleotides, chemistry, 8-Hydroxy-2'-Deoxyguanosine, biology.protein, DNA, HeLa Cells, Plasmids, Nucleotide excision repair |
| الوصف: | The in vivo mutagenicity of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) and N-(guanin-8-yl)-N-acetyl-2-aminofluorene (8-AAFdG) in human cells was determined by transfecting various cell lines with plasmids that carried a single adduct at a defined site. 8-OxodG is one of the many DNA modifications formed by oxygen radicals, and was found to be highly miscoding during replication with purified DNA polymerases in vitro. Here we show that the frequency of mutations induced by 8-oxodG during replication in vivo is at most only 2% above background. The most predominant mutation found was a single G----T transversion. The frequency of this transversion was found to be 3 to 5-fold increased in excision repair deficient XP-A cells. Interestingly, also the replication of 8-oxodG containing plasmids was significantly impaired (approximately 4-fold) in the XP-A cells, but not in HeLa cells, normal fibroblasts or XP-A revertant cells. When 8-AAFdG containing plasmids were used, the mutation frequencies did not exceed background levels (less than 2%) with any of the cell lines tested. The presence of 8-AAFdG almost completely inhibited plasmid replication (more than 50-fold) in XP-A cells. Apparently, both 8-AAFdG and 8-oxodG are not or poorly repaired in these cells, causing a block of DNA replication. This suggests that both lesions are substrates for excision repair, although to a varying extent. |
| تدمد: | 1362-4962 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a7c2831d8e9a93eedaa13ca657473589 https://doi.org/10.1093/nar/20.17.4437 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a7c2831d8e9a93eedaa13ca657473589 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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