Abstract
Replication of the oxidative lesion 8-oxo-7,8-dihydroguanine (GO) leads to the formation of both 8-oxo-7,8-dihydroguanine:adenine (GO:A) and 8-oxo-7,8-di-hydroguanine:cytosine (GO:C) pairs. The repair and mutagenic potency of these two kinds of base pairs were studied in simian COS7 and human MRC5V1 cells using the shuttle vector technology. Shuttle vectors carrying a unique GO residue opposite either a C or an A were constructed, then transfected into recipient mammalian cells. DNA repair resulting in G:C pairs and mutation frequency, were determined using resistance to digestion by the Ngo MI restriction enzyme for screening and DNA sequencing of suspect mutants. Results showed that the GO:C mismatch was well repaired since almost no mutations were detected in the plasmid progeny obtained 72 h after cell transfection. The GO:A pair was poorly repaired since only 32-34% of the plasmid progeny contained G:C whereas two thirds contained A:T at the original site. Repair kinetics measured with a non-replicating vector deleted by 13 bp at the SV40 replication origin, showed that GO:A was slowly repaired. Only 30% of the mispairs were corrected in 12 h. During this time 100% of the plasmids containing GO:A pairs were replicated as seen by the replication kinetics in a vector with an intact SV40 replication origin. These results show that, under our experimental conditions, replication is occurring before completion of DNA repair which explains the high mutagenic potency of the GO:A mispair.
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- Aburatani H., Hippo Y., Ishida T., Takashima R., Matsuba C., Kodama T., Takao M., Yasui A., Yamamoto K., Asano M. Cloning and characterization of mammalian 8-hydroxyguanine-specific DNA glycosylase/apurinic, apyrimidinic lyase, a functional mutM homologue. Cancer Res. 1997 Jun 1;57(11):2151–2156. [PubMed] [Google Scholar]
- Arai K., Morishita K., Shinmura K., Kohno T., Kim S. R., Nohmi T., Taniwaki M., Ohwada S., Yokota J. Cloning of a human homolog of the yeast OGG1 gene that is involved in the repair of oxidative DNA damage. Oncogene. 1997 Jun 12;14(23):2857–2861. doi: 10.1038/sj.onc.1201139. [DOI] [PubMed] [Google Scholar]
- Arcangeli L., Simonetti J., Pongratz C., Williams K. J. Site- and strand-specific mismatch repair of human H-ras genomic DNA in a mammalian cell line. Carcinogenesis. 1997 Jul;18(7):1311–1318. doi: 10.1093/carcin/18.7.1311. [DOI] [PubMed] [Google Scholar]
- Au K. G., Cabrera M., Miller J. H., Modrich P. Escherichia coli mutY gene product is required for specific A-G----C.G mismatch correction. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9163–9166. doi: 10.1073/pnas.85.23.9163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bodepudi V., Shibutani S., Johnson F. Synthesis of 2'-deoxy-7,8-dihydro-8-oxoguanosine and 2'-deoxy-7,8-dihydro-8-oxoadenosine and their incorporation into oligomeric DNA. Chem Res Toxicol. 1992 Sep-Oct;5(5):608–617. doi: 10.1021/tx00029a004. [DOI] [PubMed] [Google Scholar]
- Boiteux S., Gajewski E., Laval J., Dizdaroglu M. Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase): excision of purine lesions in DNA produced by ionizing radiation or photosensitization. Biochemistry. 1992 Jan 14;31(1):106–110. doi: 10.1021/bi00116a016. [DOI] [PubMed] [Google Scholar]
- Bridges B. A., Sekiguchi M., Tajiri T. Effect of mutY and mutM/fpg-1 mutations on starvation-associated mutation in Escherichia coli: implications for the role of 7,8-dihydro-8-oxoguanine. Mol Gen Genet. 1996 Jun 12;251(3):352–357. doi: 10.1007/BF02172526. [DOI] [PubMed] [Google Scholar]
- Brown T. C., Jiricny J. Different base/base mispairs are corrected with different efficiencies and specificities in monkey kidney cells. Cell. 1988 Aug 26;54(5):705–711. doi: 10.1016/s0092-8674(88)80015-1. [DOI] [PubMed] [Google Scholar]
- Bulychev N. V., Varaprasad C. V., Dormán G., Miller J. H., Eisenberg M., Grollman A. P., Johnson F. Substrate specificity of Escherichia coli MutY protein. Biochemistry. 1996 Oct 8;35(40):13147–13156. doi: 10.1021/bi960694h. [DOI] [PubMed] [Google Scholar]
- Cadet J., Berger M., Douki T., Ravanat J. L. Oxidative damage to DNA: formation, measurement, and biological significance. Rev Physiol Biochem Pharmacol. 1997;131:1–87. doi: 10.1007/3-540-61992-5_5. [DOI] [PubMed] [Google Scholar]
- Daya-Grosjean L., James M. R., Drougard C., Sarasin A. An immortalized xeroderma pigmentosum, group C, cell line which replicates SV40 shuttle vectors. Mutat Res. 1987 Mar;183(2):185–196. doi: 10.1016/0167-8817(87)90061-7. [DOI] [PubMed] [Google Scholar]
- Demple B., Harrison L. Repair of oxidative damage to DNA: enzymology and biology. Annu Rev Biochem. 1994;63:915–948. doi: 10.1146/annurev.bi.63.070194.004411. [DOI] [PubMed] [Google Scholar]
- Dizdaroglu M. Oxidative damage to DNA in mammalian chromatin. Mutat Res. 1992 Sep;275(3-6):331–342. doi: 10.1016/0921-8734(92)90036-o. [DOI] [PubMed] [Google Scholar]
- Gogos A., Cillo J., Clarke N. D., Lu A. L. Specific recognition of A/G and A/7,8-dihydro-8-oxoguanine (8-oxoG) mismatches by Escherichia coli MutY: removal of the C-terminal domain preferentially affects A/8-oxoG recognition. Biochemistry. 1996 Dec 24;35(51):16665–16671. doi: 10.1021/bi960843w. [DOI] [PubMed] [Google Scholar]
- Grollman A. P., Moriya M. Mutagenesis by 8-oxoguanine: an enemy within. Trends Genet. 1993 Jul;9(7):246–249. doi: 10.1016/0168-9525(93)90089-z. [DOI] [PubMed] [Google Scholar]
- Kasai H., Chung M. H., Jones D. S., Inoue H., Ishikawa H., Kamiya H., Ohtsuka E., Nishimura S. 8-Hydroxyguanine, a DNA adduct formed by oxygen radicals: its implication on oxygen radical-involved mutagenesis/carcinogenesis. J Toxicol Sci. 1991 Feb;16 (Suppl 1):95–105. doi: 10.2131/jts.16.supplementi_95. [DOI] [PubMed] [Google Scholar]
- Kasai H., Nishimura S. Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents. Nucleic Acids Res. 1984 Feb 24;12(4):2137–2145. doi: 10.1093/nar/12.4.2137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Le Page F., Margot A., Grollman A. P., Sarasin A., Gentil A. Mutagenicity of a unique 8-oxoguanine in a human Ha-ras sequence in mammalian cells. Carcinogenesis. 1995 Nov;16(11):2779–2784. doi: 10.1093/carcin/16.11.2779. [DOI] [PubMed] [Google Scholar]
- Lu A. L., Yuen D. S., Cillo J. Catalytic mechanism and DNA substrate recognition of Escherichia coli MutY protein. J Biol Chem. 1996 Sep 27;271(39):24138–24143. doi: 10.1074/jbc.271.39.24138. [DOI] [PubMed] [Google Scholar]
- Maki H., Sekiguchi M. MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis. Nature. 1992 Jan 16;355(6357):273–275. doi: 10.1038/355273a0. [DOI] [PubMed] [Google Scholar]
- Michaels M. L., Miller J. H. The GO system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine). J Bacteriol. 1992 Oct;174(20):6321–6325. doi: 10.1128/jb.174.20.6321-6325.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moriya M. Single-stranded shuttle phagemid for mutagenesis studies in mammalian cells: 8-oxoguanine in DNA induces targeted G.C-->T.A transversions in simian kidney cells. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1122–1126. doi: 10.1073/pnas.90.3.1122. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pletsa V., Gentil A., Margot A., Armier J., Kyrtopoulos S. A., Sarasin A. Mutagenesis by O6 meG residues within codon 12 of the human Ha-ras proto-oncogene in monkey cells. Nucleic Acids Res. 1992 Sep 25;20(18):4897–4901. doi: 10.1093/nar/20.18.4897. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Radicella J. P., Clark E. A., Chen S., Fox M. S. Patch length of localized repair events: role of DNA polymerase I in mutY-dependent mismatch repair. J Bacteriol. 1993 Dec;175(23):7732–7736. doi: 10.1128/jb.175.23.7732-7736.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Radicella J. P., Dherin C., Desmaze C., Fox M. S., Boiteux S. Cloning and characterization of hOGG1, a human homolog of the OGG1 gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010–8015. doi: 10.1073/pnas.94.15.8010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenquist T. A., Zharkov D. O., Grollman A. P. Cloning and characterization of a mammalian 8-oxoguanine DNA glycosylase. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7429–7434. doi: 10.1073/pnas.94.14.7429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sancar A. DNA repair in humans. Annu Rev Genet. 1995;29:69–105. doi: 10.1146/annurev.ge.29.120195.000441. [DOI] [PubMed] [Google Scholar]
- Shibutani S., Takeshita M., Grollman A. P. Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG. Nature. 1991 Jan 31;349(6308):431–434. doi: 10.1038/349431a0. [DOI] [PubMed] [Google Scholar]
- Slupska M. M., Baikalov C., Luther W. M., Chiang J. H., Wei Y. F., Miller J. H. Cloning and sequencing a human homolog (hMYH) of the Escherichia coli mutY gene whose function is required for the repair of oxidative DNA damage. J Bacteriol. 1996 Jul;178(13):3885–3892. doi: 10.1128/jb.178.13.3885-3892.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Stary A., Sarasin A. Simian virus 40 (SV40) large T antigen-dependent amplification of an Epstein-Barr virus-SV40 hybrid shuttle vector integrated into the human HeLa cell genome. J Gen Virol. 1992 Jul;73(Pt 7):1679–1685. doi: 10.1099/0022-1317-73-7-1679. [DOI] [PubMed] [Google Scholar]
- Tsai-Wu J. J., Liu H. F., Lu A. L. Escherichia coli MutY protein has both N-glycosylase and apurinic/apyrimidinic endonuclease activities on A.C and A.G mispairs. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8779–8783. doi: 10.1073/pnas.89.18.8779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsai-Wu J. J., Lu A. L. Escherichia coli mutY-dependent mismatch repair involves DNA polymerase I and a short repair tract. Mol Gen Genet. 1994 Aug 15;244(4):444–450. doi: 10.1007/BF00286698. [DOI] [PubMed] [Google Scholar]
- Wallace S. S. DNA damages processed by base excision repair: biological consequences. Int J Radiat Biol. 1994 Nov;66(5):579–589. doi: 10.1080/09553009414551661. [DOI] [PubMed] [Google Scholar]
- Xu J. F., Yang Q. P., Chen J. Y., van Baalen M. R., Hsu I. C. Determining the site and nature of DNA mutations with the cloned MutY mismatch repair enzyme. Carcinogenesis. 1996 Feb;17(2):321–326. doi: 10.1093/carcin/17.2.321. [DOI] [PubMed] [Google Scholar]
- Zhang X., Rosenstein B. S., Wang Y., Lebwohl M., Mitchell D. M., Wei H. Induction of 8-oxo-7,8-dihydro-2'-deoxyguanosine by ultraviolet radiation in calf thymus DNA and HeLa cells. Photochem Photobiol. 1997 Jan;65(1):119–124. doi: 10.1111/j.1751-1097.1997.tb01886.x. [DOI] [PubMed] [Google Scholar]
- van der Kemp P. A., Thomas D., Barbey R., de Oliveira R., Boiteux S. Cloning and expression in Escherichia coli of the OGG1 gene of Saccharomyces cerevisiae, which codes for a DNA glycosylase that excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5197–5202. doi: 10.1073/pnas.93.11.5197. [DOI] [PMC free article] [PubMed] [Google Scholar]