Cited by 82DNA Repair MechanismsCarcinogens and Genotoxicity AssessmentMitochondrial Function and Pathology

DNA repair of UV photoproducts and mutagenesis in human mitochondrial DNA

Pascucci, B., Versteegh, A., van Hoffen, A., van Zeeland, A.A., Mullenders, L.H.F., Dogliotti, E.·1997·Journal of Molecular Biology

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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Crossref · 10.1006/jmbi.1997.1268

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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)
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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