DNA repair of UV photoproducts and mutagenesis in human mitochondrial DNA
Abstract
The induction and repair of DNA photolesions and mutations in the mitochondrial (mt) DNA of human cells in culture were analysed after cell exposure to UV-C light. The level of induction of cyclobutane pyrimidine dimers (CPD) in mitochondrial and nuclear DNA was comparable, while a higher frequency of pyrimidine (6-4) pyrimidone photoproducts (6-4 PP) was detected in mitochondrial than in nuclear DNA. Besides the known defect in CPD removal, mitochondria were shown to be deficient also in the excision of 6-4 PP. The effects of repair-defective conditions for the two major UV photolesions on mutagenesis was assessed by analysing the frequency and spectrum of spontaneous and UV-induced mutations by restriction site mutation (RSM) method in a restriction endonuclease site, NciI (5'CCCGG3') located within the coding sequence of the mitochondrial gene for tRNALeu. The spontaneous mutation frequency and spectrum at the NciI site of mitochondrial DNA was very similar to the RSM background mutation frequency (approximately 10(-5)) and type (predominantly GC>AT transitions at G1 of the NciI site). Conversely, an approximately tenfold increase over background mutation frequency was recorded after cell exposure to 20 J/m2. In this case, the majority of mutations were C>T transitions preferentially located on the non-transcribed DNA strand at C1 and C2 of the NciI site. This mutation spectrum is expected by UV mutagenesis. This is the first evidence of induction of mutations in mitochondrial DNA by treatment of human cells with a carcinogen.
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Mitochondria do not exhibit NER activity, and thus removal of photoproducts can be significantly reduced.
“Surprisingly, mitochondria do not exhibit NER activity and thus the removal of photoproducts can be significantly reduced [141,144].”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [144]
Cites
1 retracted
High levels of genetic change in rodents of Chernobyl
Barker, R. J., Bussche, R. A. V. D., Wright, A. J., et al. (1996) · Nature · doi:10.1038/380707a0 · Cited by 76 · see citing works
RetractedDNA sequencing with chain-terminating inhibitors
Sanger, F., Nicklen, S., & Coulson, A. R. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.12.5463 · Cited by 68,572 · see citing works
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
Feinberg, A. P., & Vogelstein, B. (1983) · Analytical Biochemistry · doi:10.1016/0003-2697(83)90418-9 · Cited by 24,512 · see citing works
Rapid evolution of animal mitochondrial DNA
Brown, W. M., George, M., & Wilson, A. C. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.4.1967 · Cited by 3,439 · see citing works
Normal oxidative damage to mitochondrial and nuclear DNA is extensive.
Richter, C., Park, J. W., & Ames, B. N. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.17.6465 · Cited by 1,730 · see citing works
Replication of animal mitochondrial DNA
Clayton, D. A. (1982) · Cell · doi:10.1016/0092-8674(82)90049-6 · Cited by 1,236 · see citing works
Analysis of Mutation in Human Cells by Using an Epstein-Barr Virus Shuttle System
DuBridge, R. B., Tang, P., Hsia, H. C., Leong-Morgenthaler, P.-M., Miller, J. H., & Calos, M. P. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.1.379 · Cited by 1,134 · see citing works
PCR fidelity of pfu DNA polymerase and other thermostable DNA polymerases
Cline, J. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.18.3546 · Cited by 720 · see citing works
Jenuth, J. P., Peterson, A. C., Fu, K., & Shoubridge, E. A. (1996) · Nature Genetics · doi:10.1038/ng1096-146 · Cited by 591 · see citing works
Mitochondrial mutations may increase oxidative stress: Implications for carcinogenesis and aging?
Bandy, B., & Davison, A. J. (1990) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(90)90152-9 · Cited by 550 · see citing works
The Absence of a Pyrimidine Dimer Repair Mechanism in Mammalian Mitochondria
Clayton, D. A., Doda, J. N., & Friedberg, E. C. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.7.2777 · Cited by 531 · see citing works
Mitochondrial DNA sequence variation in human evolution and disease.
Wallace, D. C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.8739 · Cited by 520 · see citing works
MOLECULAR GENETIC ASPECTS OF HUMAN MITOCHONDRIAL DISORDERS
Larsson, N.-G., & Clayton, D. A. (1995) · Annual Review of Genetics · doi:10.1146/annurev.ge.29.120195.001055 · Cited by 493 · see citing works
Chomyn, A., Martinuzzi, A., Yoneda, M., Daga, A., Hurko, O., Johns, D. R., Lai, S. T., Nonaka, I., Angelini, C. I., & Attardi, G. M. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.10.4221 · Cited by 491 · see citing works
Aguilar, F., Hussain, S. P., & Cerutti, P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.18.8586 · Cited by 490 · see citing works
Venema, J., van Hoffen, A., Karcagi, V., Natarajan, A. T., van Zeeland, A. A., & Mullenders, L. H. F. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.8.4128 · Cited by 317 · see citing works
Self-citationKruse, B., Narasimhan, N., & Attardi, G. M. (1989) · Cell · doi:10.1016/0092-8674(89)90853-2 · Cited by 311 · see citing works
The development of mitochondrial medicine.
Luft, R. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.8731 · Cited by 302 · see citing works
Repair of mitochondrial DNA after various types of DNA damage in Chinese hamster ovary cells
LeDoux, S. P., Wilson, G. L., Beecham, E. J., Stevnsner, T., Wassermann, K., & Bohr, V. A. (1992) · Carcinogenesis · doi:10.1093/carcin/13.11.1967 · Cited by 269 · see citing works
van Hoffen, A., Venema, J., Meschini, R., van Zeeland, A. A., & Mullenders, L. H. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07010.x · Cited by 242 · see citing works
Self-citationSage, É. (1993) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1993.tb02273.x · Cited by 235 · see citing works
Backer, J. M., & Weinstein, I. B. (1980) · Science · doi:10.1126/science.6770466 · Cited by 230 · see citing works
A nuclear 'fossil' of the mitochondrial D-loop and the origin of modern humans
Zischler, H., Geisert, H., von Haeseler, A., & Pääbo, S. (1995) · Nature · doi:10.1038/378489a0 · Cited by 230 · see citing works
Strand Asymmetry in Human Mitochondrial DNA Mutations
Tanaka, M., & Ozawa, T. (1994) · Genomics · doi:10.1006/geno.1994.1391 · Cited by 205 · see citing works
Covalent binding of polycyclic aromatic compounds to mitochondrial and nuclear DNA
Allen, J. A., & Coombs, M. M. (1980) · Nature · doi:10.1038/287244a0 · Cited by 203 · see citing works
Preferential Attack of Mitochondrial DNA by Aflatoxin B 1 During Hepatocarcinogenesis
Niranjan, B. G., Bhat, N. K., & Avadhani, N. G. (1982) · Science · doi:10.1126/science.6797067 · Cited by 188 · see citing works
Kalinowski, D. P., Illenye, S. A., & Houten, B. V. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.13.3485 · Cited by 165 · see citing works
Mitchell, D. L., Nguyen, T., & Cleaver, J. E. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39363-9 · Cited by 141 · see citing works
Are mitochondrial DNA mutations involved in the carcinogenic process?
Shay, J. W., & Werbin, H. (1987) · Mutation Research/Reviews in Genetic Toxicology · doi:10.1016/0165-1110(87)90028-5 · Cited by 132 · see citing works
Action of Mitochondrial DNA Polymerase γ at Sites of Base Loss or Oxidative Damage
Pinz, K. G., Shibutani, S., & Bogenhagen, D. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.16.9202 · Cited by 126 · see citing works
Svoboda, D. L., & Vos, J. M. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.26.11975 · Cited by 111 · see citing works
Blanc, H., Wright, C. T., Bibb, M. J., et al. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.6.3789 · Cited by 107 · see citing works
A Tridecamer DNA Sequence Supports Human Mitochondrial RNA 3′-End Formation In Vitro
Christianson, T. W., & Clayton, D. A. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.10.4502-4509.1988 · Cited by 102 · see citing works
Balansky, R. M., Izzotti, A., Scatolini, L., D’Agostini, F., & Flora, S. D. (1996) · PubMed · Cited by 90 · see citing works
Mammalian mitochondrial endonuclease activities specific for ultraviolet-irradiated DNA
Tomkinson, A. E., Bonk, R. T., Kim, J., et al. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.4.929 · Cited by 81 · see citing works
Chloramphenicol‐resistant mutants of human HeLa cells
Spolsky, C., & Eisenstadt, J. M. (1972) · FEBS Letters · doi:10.1016/0014-5793(72)80514-3 · Cited by 78 · see citing works
Preferential binding of cisplatin to mitochondrial DNA of Chinese hamster ovary cells
Olivero, O. A., Semino, C., Kassim, A., et al. (1995) · Mutation Research Letters · doi:10.1016/0165-7992(95)90039-x · Cited by 74 · see citing works
Mutagenesis of the H-ras protooncogene and the p53 tumor suppressor gene.
Cerutti, P., Hussain, S. P., Pourzand, C., et al. (1994) · PubMed · Cited by 71 · see citing works
Cummings, O. W., King, T. C., Holden, J. A., et al. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61611-4 · Cited by 65 · see citing works
A tridecamer DNA sequence supports human mitochondrial RNA 3'-end formation in vitro.
Christianson, T. W., & Clayton, D. A. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.10.4502 · Cited by 58 · see citing works
Slott, E. F., Shade, R. O., & Lansman, R. A. (1983) · Molecular and Cellular Biology · doi:10.1128/mcb.3.10.1694 · Cited by 44 · see citing works
Resistance of HeLa cell mitochondrial DNA to mutagenesis by chemical carcinogens.
Mita, S., Monnat, R. J., & Loeb, L. A. (1988) · PubMed · Cited by 38 · see citing works
Mutagenesis of codon 248 of the human p53 tumor suppressor gene by N-ethyl-N-nitrosourea.
Hussain, S. P., Aguilar, F., & Cerutti, P. (1994) · PubMed · Cited by 36 · see citing works
Evolutionary trail of the mitochondrial genome as based on human 16S rDNA pseudogenes
Hu, G., & Thilly, W. G. (1994) · Gene · doi:10.1016/0378-1119(94)90065-5 · Cited by 34 · see citing works
N-methyl-N-nitrosourea-induced mutations in human cells
Palombo, F., Kohfeldt, E., Calcagnile, A. S., Nehls, P., & Eugenia Dogliotti, Y. (1992) · Journal of Molecular Biology · doi:10.1016/0022-2836(92)90974-o · Cited by 30 · see citing works
Cytoplasmic inheritance of oligomycin resistance in Chinese hamster ovary cells.
Breen, G. A. M., & Scheffler, I. E. (1980) · The Journal of Cell Biology · doi:10.1083/jcb.86.3.723 · Cited by 28 · see citing works
Chiocca, S., Sandy, M. S., & Cerutti, P. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5331 · Cited by 27 · see citing works
Wallace, D. C., & Eisenstadt, J. M. (1979) · Somatic Cell and Molecular Genetics · doi:10.1007/bf01538849 · Cited by 26 · see citing works
Hu, G., & Thilly, W. G. (1995) · Current Genetics · doi:10.1007/bf00310808 · Cited by 21 · see citing works
Screening for human mitochondrial DNA polymorphisms with denaturing gradient gel electrophoresis
Hanekamp, J. S., Thilly, W. G., & Chaudhry, M. A. (1996) · Human Genetics · doi:10.1007/s004390050201 · Cited by 19 · see citing works
Development of new molecular procedures for the detection of genetic alterations in man
Steingrimsdottir, H., Beare, D. M., Cole, J., et al. (1996) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(95)00244-8 · Cited by 17 · see citing works
Mitochondrial DNA gets the drift
Clayton, D. A. (1996) · Nature Genetics · doi:10.1038/ng1096-123 · Cited by 14 · see citing works
Non-phenotypic selection of N-methyl-N-nitrosourea-induced mutations in human cells
Palombo, F., Bignami, M., & Dogliotti, E. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.6.1349 · Cited by 13 · see citing works
Self-citationStrand bias of ultraviolet light‐induced mutations in a transcriptionally active gene in human cells
Bašić-Zaninović, T., Meschini, R., Calcagnile, A. S., Palombo, F., D’Errico, M., Sanctis, L. P., & Eugenia Dogliotti, Y. (1995) · Molecular Carcinogenesis · doi:10.1002/mc.2940140311 · Cited by 12 · see citing works
U.v.-hypermutability of xeroderma pigmentosum cells demonstrated with a DNA-based mutation system.
Steingrimsdottir, H., Beare, D., Carr, A. M., Cole, J., & Ar, L. (1995) · PubMed · Cited by 11 · see citing works
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Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies
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Rochette, P. J., & Brash, D. E. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000926 · Cited by 133 · see citing works
- Authors
- Pascucci, B., Versteegh, A., van Hoffen, A., van Zeeland, A. A., Mullenders, L. H. F., & Dogliotti, E.
- Affiliations
- Istituto Superiore di Sanità (IT)
- Leiden University (NL)
- ORCID
- Pascucci, B.
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 1997-10
- Volume
- 273
- Issue
- 2
- Pages
- 417-427
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W1965126369
- Cited by
- 82
- References
- 55
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 1 · 2012: 4
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitochondrial DNA, UV mutagenesis, UV-C light, cyclobutane pyrimidine dimers, 6-4 pyrimidone photoproducts, DNA repair, restriction site mutations, tRNALeu, mutation spectrum, spontaneous mutation, human cells
- MeSH terms
- Base Sequence, Cell Nucleus, Cells, Cultured, DNA Repair, DNA, Mitochondrial, Dose-Response Relationship, Radiation, Fibroblasts, Humans, Molecular Sequence Data, Pyrimidine Dimers, Polymorphism, Restriction Fragment Length, Ultraviolet Rays, Deoxyribonucleases, Type II Site-Specific, Polymerase Chain Reaction, Mutagenesis
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