The fidelity of the human leading and lagging strand DNA replication apparatus with 8-oxodeoxyguanosine triphosphate
Open accessAbstract
A product of oxidative metabolism, 8-oxodeoxyguanosine triphosphate (8-O-dGTP), readily pairs with adenine during DNA replication, ultimately causing A.T-->C.G transversions. This study utilized 8-O-dGTP as a probe to examine the fidelity of the leading and lagging strand replication apparatus in extracts of HeLa cells. Simian virus (SV) 40 T antigen-dependent DNA replication reactions were performed with two M13mp2 vectors with the SV40 origin located on opposite sides of the lacZ alpha sequence used to score replication errors. The presence of 8-O-dGTP at equimolar concentration with each of the 4 normal dNTPs resulted in a > 46-fold increase in error rate for A.T-->C.G transversion over that observed in the absence of 8-O-dGTP. A similar average error rate was observed on the (+) and (-) strands in both vectors, suggesting that the fidelity of replication by leading and lagging strand replication proteins is similar for the dA.8-O-dGMP mispair. Replication fidelity in the presence of 8-O-dGTP was reduced on both strands when an inhibitor of exonucleolytic proofreading (dGMP) was added to the reaction. These data suggest that the majority of dA.8-O-dGMP mispairs are proofread by both leading and lagging strand replication proteins.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
MtDNA oxidation renders mtDNA more susceptible to mutation because oxidized bases are misread during replication and lead to nucleotide substitutions.
“MtDNA oxidation, in turn, renders mtDNA more susceptible to mutation because oxidized bases are misread during replication and this leads to nucleotide substitutions [118–120].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [118]
Cites
Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG
Shibutani, S., Takeshita, M., & Grollman, A. P. (1991) · Nature · doi:10.1038/349431a0 · Cited by 2,224 · see citing works
8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G-T and A-C substitutions.
Cheng, K. C., Cahill, D. S., Kasai, H., Nishimura, S., & Loeb, L. A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48474-8 · Cited by 1,844 · see citing works
MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis
Maki, H., & Sekiguchi, M. (1992) · Nature · doi:10.1038/355273a0 · Cited by 891 · see citing works
Mutagenesis by 8-oxoguanine: an enemy within
Grollman, A. P., & Moriya, M. (1993) · Trends in Genetics · doi:10.1016/0168-9525(93)90089-z · Cited by 807 · see citing works
Michaels, M. L., & Miller, J. H. (1992) · Journal of Bacteriology · doi:10.1128/jb.174.20.6321-6325.1992 · Cited by 693 · see citing works
Anatomy of a DNA replication fork revealed by reconstitution of SV40 DNA replication in vitro
Waga, S., & Stillman, B. (1994) · Nature · doi:10.1038/369207a0 · Cited by 557 · see citing works
EUKARYOTIC CHROMOSOME REPLICATION
Edenberg, H. J., & Huberman, J. A. (1975) · Annual Review of Genetics · doi:10.1146/annurev.ge.09.120175.001333 · Cited by 449 · see citing works
Sakumi, K., Furuichi, M., Tsuzuki, T., Kakuma, T., KAWABATA, S., Maki, H., & Sekiguchi, M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49494-5 · Cited by 435 · see citing works
Reconstitution of complete SV40 DNA replication with purified replication factors.
Waga, S., Bauer, G. A., & Stillman, B. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34146-7 · Cited by 404 · see citing works
Mo, J. Y., Maki, H., & Sekiguchi, M. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.11021 · Cited by 312 · see citing works
Kouchakdjian, M., Bodepudi, V., Shibutani, S., Eisenberg, M., Johnson, F., Grollman, A. P., & Patel, D. J. (1991) · Biochemistry · doi:10.1021/bi00219a034 · Cited by 298 · see citing works
Hay, R. T., & DePamphilis, M. L. (1982) · Cell · doi:10.1016/0092-8674(82)90056-3 · Cited by 259 · see citing works
The in vitro replication of DNA containing the SV40 origin.
Hurwitz, J., Dean, F. B., Kwong, A. D., & Lee, S. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44708-9 · Cited by 255 · see citing works
Li, J. J., & Kelly, T. J. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.6.1238 · Cited by 205 · see citing works
Kunkel, T. A. (1988) · Cell · doi:10.1016/s0092-8674(88)90189-4 · Cited by 134 · see citing works
Self-citationDNA replication fidelity with 8-oxodeoxyguanosine triphosphate
Pavlov, Y. I., Minnick, D. T., Izuta, S., & Kunkel, T. A. (1994) · Biochemistry · doi:10.1021/bi00181a029 · Cited by 132 · see citing works
Self-citationFidelity of mammalian DNA replication and replicative DNA polymerases
Thomas, D. C., Roberts, J. D., Sabatino, R. D., Myers, T. W., Tan, C. K., Downey, K. M., So, A. G., Bambara, R. A., & Kunkel, T. A. (1991) · Biochemistry · doi:10.1021/bi00115a003 · Cited by 121 · see citing works
Self-citationProperties of DNA polymerases δ and ϵ, and their roles in eukaryotic DNA replication
Bambara, R. A., & Jessee, C. B. (1991) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(91)90147-e · Cited by 116 · see citing works
Fidelity of a human cell DNA replication complex.
Roberts, J. D., & Kunkel, T. A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.19.7064 · Cited by 92 · see citing works
Self-citationLi, J. J., & Kelly, T. J. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.6.1238-1246.1985 · Cited by 85 · see citing works
Sequence specificity for the initiation of RNA-primed simian virus 40 DNA synthesis in vivo
Hay, R. T., Hendrickson, E. A., & DePamphilis, M. L. (1984) · Journal of Molecular Biology · doi:10.1016/0022-2836(84)90471-6 · Cited by 78 · see citing works
Exonucleolytic proofreading of leading and lagging strand DNA replication errors.
Roberts, J. D., Thomas, D. C., & Kunkel, T. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.8.3465 · Cited by 57 · see citing works
Self-citationThomas, D. C., & Kunkel, T. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.16.7744 · Cited by 55 · see citing works
Self-citationFrameshift fidelity during replication of double-stranded DNA in HeLa cell extracts
Roberts, J. D., Dinh, N., & Kunkel, T. A. (1993) · Biochemistry · doi:10.1021/bi00066a033 · Cited by 40 · see citing works
Self-citationRoberts, J. D., Izuta, S., Thomas, D. C., & Kunkel, T. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42086-2 · Cited by 36 · see citing works
Self-citationThomas, D. C., Nguyen, D. C., Piegorsch, W. W., & Kunkel, T. A. (1993) · Biochemistry · doi:10.1021/bi00094a002 · Cited by 35 · see citing works
Self-citationLee, Y. S., Lee, H. S., Park, M. K., Hwang, E. S., Park, E. M., Kasai, H., & Chung, M. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.2427 · Cited by 29 · see citing works
Zhang, S.-S., & Große, F. (1990) · Journal of Molecular Biology · doi:10.1016/0022-2836(90)90370-2 · Cited by 25 · see citing works
Fidelity of DNA replication by extracts of normal and malignantly transformed human cells.
Boyer, J. C., Thomas, D. C., Maher, V. M., McCormick, J. J., & Kunkel, T. A. (1993) · PubMed · Cited by 20 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Mutagenicity, toxicity and repair of DNA base damage induced by oxidation
Bjelland, S., & Seeberg, E. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.07.002 · Cited by 510 · see citing works
Brain aging, Alzheimer's disease, and mitochondria
Swerdlow, R. H. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.08.012 · Cited by 306 · see citing works
“MtDNA oxidation, in turn, renders mtDNA more susceptible to mutation because oxidized bases are misread during replication and this leads to nucleotide substitutions [118–120].”
BackgroundStrand asymmetries in DNA evolution
Francino, M. P., & Ochman, H. (1997) · Trends in Genetics · doi:10.1016/s0168-9525(97)01118-9 · Cited by 264 · see citing works
Oxidative nucleotide damage: consequences and prevention
Sekiguchi, M., & Tsuzuki, T. (2002) · Oncogene · doi:10.1038/sj.onc.1206023 · Cited by 229 · see citing works
Oxidative damage to purines in DNA: Role of mammalian Ogg1
Klungland, A., & Bjelland, S. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.10.012 · Cited by 150 · see citing works
Oxidative DNA damage in cancer patients: a cause or a consequence of the disease development?
Oliński, R., Gackowski, D., Różalski, R., Foksiński, M., & Białkowski, K. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.07.005 · Cited by 121 · see citing works
Inoue, M., Kamiya, H., Fujikawa, K., Ootsuyama, Y., Murata‐Kamiya, N., Osaki, T., Yasumoto, K., & Kasai, H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.18.11069 · Cited by 109 · see citing works
DNA repair and the origins of urinary oxidized 2'-deoxyribonucleosides
Evans, M. D., Saparbaev, M. K., & Cooke, M. S. (2010) · Mutagenesis · doi:10.1093/mutage/geq031 · Cited by 93 · see citing works
8-Oxoguanine incorporation into DNA repeats in vitro and mismatch recognition by MutS
Macpherson, P. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki813 · Cited by 73 · see citing works
Fujikawa, K., Kamiya, H., & Kasai, H. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.20.4582 · Cited by 69 · see citing works
Alzheimer’s Disease Pathologic Cascades: Who Comes First, What Drives What
Swerdlow, R. H. (2011) · Neurotoxicity Research · doi:10.1007/s12640-011-9272-9 · Cited by 66 · see citing works
Pathways controlling dNTP pools to maintain genome stability
Rudd, S. G., Valerie, N. C. K., & Helleday, T. (2016) · DNA repair · doi:10.1016/j.dnarep.2016.05.032 · Cited by 63 · see citing works
Armstrong, M. J., & Galloway, S. M. (1997) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(96)00234-5 · Cited by 58 · see citing works
Stone, J. E., Lujan, S. A., & Kunkel, T. A. (2012) · Environmental and Molecular Mutagenesis · doi:10.1002/em.21728 · Cited by 57 · see citing works
Self-citationInvolvement of DNA polymerase β in DNA replication and mutagenic consequences
Servant, L., Bieth, A., Hayakawa, H., Cazaux, C., & Hoffmann, J. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5307 · Cited by 53 · see citing works
Tassotto, M. L., & Mathews, C. K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200965200 · Cited by 44 · see citing works
Non-canonical actions of mismatch repair
Crouse, G. F. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.11.020 · Cited by 43 · see citing works
Larson, E. D., Iams, K. P., & Drummond, J. T. (2003) · DNA repair · doi:10.1016/s1568-7864(03)00140-x · Cited by 37 · see citing works
Swerdlow, R. H. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.3948 · Cited by 35 · see citing works
Thomas, D. C., Veaute, X., Fuchs, R. P., & Kunkel, T. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.36.21226 · Cited by 27 · see citing works
Self-citationArczewska, K. D., & Kuśmierek, J. T. (2007) · Acta Biochimica Polonica · doi:10.18388/abp.2007_3220 · Cited by 23 · see citing works
Somatic genetic aberrations in benign breast disease and the risk of subsequent breast cancer
Zeng, Z., Vo, A. H., Li, X., Shidfar, A., Saldana, P., Blanco, L. Z., Xuei, X., Luo, Y., Khan, S. A., & Clare, S. E. (2020) · npj Breast Cancer · doi:10.1038/s41523-020-0165-z · Cited by 18 · see citing works
DNA polymerase mutagenic bypass and proofreading of endogenous DNA lesions
Eckert, K. A., & Opresko, P. L. (1999) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(99)00021-4 · Cited by 19 · see citing works
Nelson, S. R., Kathe, S. D., Hilzinger, T. S., Averill, A. M., Warshaw, D. M., Wallace, S. S., & Lee, A. J. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz045 · Cited by 16 · see citing works
Bębenek, K., Boyer, J. C., & Kunkel, T. A. (1999) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(99)00119-0 · Cited by 16 · see citing works
Self-citation7 Fidelity of DNA ReplicationPreprint
Roberts, J. D., & Kunkel, T. A. (1996) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969459.31.217 · Cited by 16 · see citing works
Self-citationMisincorporation rate and type on the leading and lagging strands of UV- damaged DNA
Calcagnile, A. S. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.15.3005 · Cited by 13 · see citing works
Specialized mismatch repair function of Glu339 in the Phe-X-Glu motif of yeast Msh6
Holmes, S. F., Scarpinato, K. D., McCulloch, S. D., Schaaper, R. M., & Kunkel, T. A. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.10.023 · Cited by 12 · see citing works
Self-citationBiałkowski, K., & Kasprzak, K. S. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.07.018 · Cited by 8 · see citing works
Mourgues, S., Trzcionka, J., Vasseur, J., Pratviel, G., & Meunier, B. (2008) · Biochemistry · doi:10.1021/bi7022199 · Cited by 7 · see citing works
Cheng, Y., Wang, X., Yang, X., Zhang, Y., & You, H. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf508 · Cited by 3 · see citing works
Roberts, J. D., & Kunke, T. A. (1996)
Genetic stability in the hyperthermophilic archaeon Sulfolobus acidocaldarius
Cong, X. (2015) · OhioLink ETD Center (Ohio Library and Information Network)
Mutational Processes Modeling and Early Cancer Diagnosis
Zeng, Z. (2019) · Swiss Medical Weekly · doi:10.21985/n2-8smw-1121
- Authors
- Minnick, D. T., Pavlov, Y. I., & Kunkel, T. A.
- Affiliations
- National Institutes of Health (US)
- St Petersburg University (RU)
- Corresponding author
- Kunkel, Thomas A.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1994
- Volume
- 22
- Issue
- 25
- Pages
- 5658-5664
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC310130
- OpenAlex
- W2085060564
- Cited by
- 34
- References
- 28
- Citations by year
- 2025: 1 · 2020: 1 · 2019: 2 · 2016: 1 · 2015: 2 · 2012: 1
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nucleic Acids Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- DNA replication fidelity, leading strand, lagging strand, oxidative DNA damage, exonuclease proofreading, SV40 T antigen, HeLa cells, dGMP
- MeSH terms
- Base Sequence, Deoxyguanine Nucleotides, DNA Repair, DNA Replication, Exonucleases, HeLa Cells, Humans, Molecular Sequence Data, Oxidation-Reduction, Mutagenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
