Differential repair of UVB-induced cyclobutane pyrimidine dimers in cultured human skin cells and whole human skin

Mouret, Stéphane; Charveron, Marie; Favier, Alain; Cadet, Jean; Douki, Thierry

doi:10.1016/j.dnarep.2008.01.005

Cited by 92DNA Repair MechanismsSkin Protection and AgingCarcinogens and Genotoxicity Assessment

Differential repair of UVB-induced cyclobutane pyrimidine dimers in cultured human skin cells and whole human skin

Mouret, Stéphane, Charveron, Marie, Favier, Alain, Cadet, Jean, Douki, Thierry·2008·DNA Repair

DOI 10.1016/j.dnarep.2008.01.005

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Abstract

Cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) are the two main classes of mutagenic DNA damages induced by UVB radiation. Numerous studies have been devoted so far to their formation and repair in human cells and skin. However, the biochemical methods used often lack the specificity that would allow the individual study of each of the four CPDs and 6-4PPs produced at TT, TC, CT and CC dinucleotides. In the present work, we applied an HPLC-mass spectrometry assay to study the formation and repair of CPDs and 6-4PPs photoproducts in primary cultures of human keratinocytes and fibroblasts as well as in whole human skin. We first observed that the yield of dimeric lesions was slightly higher in fibroblasts than in keratinocytes. In contrast, the rate of global repair was higher in the last cell type. Moreover, removal of DNA photoproducts in skin biopsies was found to be slower than in both cultured skin cells. In agreement with previous works, the repair of 6-4PPs was found to be more efficient than that of CPDs in the three types of samples, with no observed difference between the removal of the TT and TC derivatives. In contrast, a significant influence of the nature of the two modified pyrimidines was observed on the repair rate of CPDs. The decreasing order of removal efficiency was the following: C<>T>C<>C>T<>C>T<>T. These data, together with the known intrinsic mutational properties of the lesions, would support the reported UV mutation spectra. A noticeable exception concerns CC dinucleotides that are mutational hotspots with an UV-specific CC to TT tandem mutation, although related bipyrimidine photoproducts are produced in low yields and efficiently repaired.

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The four CPDs are repaired at different rates, with increasing efficiency in the order T<>T < T<>C < C<>C < C<>T.
“HPLC-ESI-MS ⁄ MS measurement also revealed that the four CPDs were not repaired with the same rate, being enzymatically removed in the following increasing order of efficiency: T< >T < T<>C < C<>C C<>T (49).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions† (2012) · cites this paper as [49]

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Authors: Mouret, S., Charveron, M., Favier, A., Cadet, J., & Douki, T.
Affiliations: Université Joseph Fourier (FR)
Corresponding author: Douki, Thierry
ORCID: Mouret, Stéphane
Favier, Alain
Cadet, Jean
Douki, Thierry
Venue: DNA Repair
Publisher: Elsevier BV
Published: 2008-05
Volume: 7
Issue: 5
Pages: 704-712
ISSN: 1568-7856 (ISSN-L)
1568-7864
DOI: 10.1016/j.dnarep.2008.01.005
OpenAlex: W1981121984
Cited by: 92
References: 56
Citations by year: 2026: 3 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 9 · 2020: 8 · 2019: 7 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 6 · 2013: 10 · 2012: 6
FWCI: 2.61
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: DNA repair (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Health Sciences › Medicine › Dermatology › Skin Protection and Aging
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords: cyclobutane pyrimidine dimers, 6-4 pyrimidone photoproducts, UVB-induced DNA damage, human keratinocytes, fibroblasts, human skin
MeSH terms: Cells, Cultured, DNA Repair, Fibroblasts, Humans, Kinetics, Organ Culture Techniques, Pyrimidine Dimers, Skin, Ultraviolet Rays, Keratinocytes

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Differential repair of UVB-induced cyclobutane pyrimidine dimers in cultured human skin cells and whole human skin

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