Repair of the three main types of bipyrimidine DNA photoproducts in human keratinocytes exposed to UVB and UVA radiations

Courdavault, Sophie; Baudouin, C.; Charvéron, M.; Canguilhem, Bruno; Favier, Alain; Cadet, Jean; Douki, Thierry

doi:10.1016/j.dnarep.2005.05.001

Cited by 137 publications

(160 citation statements)

References 52 publications

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“…In contrast, the removal of CPDs from both tissues is gradual for the first 24 h. Although more than 80% of CPDs are removed from epidermal cells within 5 days, less than 50% of CPDs are removed from dermal fibroblasts during this time. These characteristics of skin tissues in the removal of UV lesions are consistent with the repair rates of UV lesions observed in mouse and human cultured epidermal keratinocytes and dermal fibroblasts (11,12,14,46,52). Accordingly, the repair rate of (6-4)PPs is similar for the two cell types, whereas CPDs are removed significantly faster from keratinocytes than from fibroblasts.…”

Section: Role For Pol In Prevention Of Uv-induced Mesenchymal Tumorssupporting

confidence: 65%

“…A quantitative analysis of dipyrimidine photoproducts using a high-performance liquid chromatography-tandem mass spectrometry system was performed on DNA from UV-B-irradiated human fibroblasts (11,12). According to these reports, in the case of CPDs the formation of thymine-thymine photoproducts was twice that of thyminecytosine photoproducts.…”

Section: Role For Pol In Prevention Of Uv-induced Mesenchymal Tumorsmentioning

confidence: 99%

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UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

Ohkumo

Kondo

Yokoi

et al. 2006

Molecular and Cellular Biology

107

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DNA polymerase(Pol ) is the product of the Polh gene, which is responsible for the group variant of xeroderma pigmentosum, a rare inherited recessive disease which is characterized by susceptibility to sunlightinduced skin cancer. We recently reported in a study of Polh mutant mice that Pol is involved in the somatic hypermutation of immunoglobulin genes, but the cancer predisposition of Polh ؊/؊ mice has not been examined until very recently. Another translesion synthesis polymerase, Pol , a Pol paralog encoded by the Poli gene, is naturally deficient in the 129 mouse strain, and the function of Pol is enigmatic. Here, we generated Polh Poli doubledeficient mice and compared the tumor susceptibility of them with Polh-or Poli-deficient animals under the same genetic background. While Pol deficiency does not influence the UV sensitivity of mouse fibroblasts irrespective of Polh genotype, Polh Poli double-deficient mice show slightly earlier onset of skin tumor formation. Intriguingly, histological diagnosis after chronic treatment with UV light reveals that Pol deficiency leads to the formation of mesenchymal tumors, such as sarcomas, that are not observed in Polh ؊/؊ mice. These results suggest the involvement of the Pol and Pol proteins in UV-induced skin carcinogenesis.

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Section: Role For Pol In Prevention Of Uv-induced Mesenchymal Tumorssupporting

confidence: 65%

Section: Role For Pol In Prevention Of Uv-induced Mesenchymal Tumorsmentioning

confidence: 99%

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

Ohkumo

Kondo

Yokoi

et al. 2006

Molecular and Cellular Biology

107

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“…We could therefore estimate that the formation of 4 in cells treated with bleomycin is not a minor pathway. The kinetic of removal of 4 in cellular DNA is almost similar to that determined for bulky DNA adduct such as UV-induced DNA bipyrimidine lesions that are known to be repaired by the nucleotide excision repair pathway (37). However, additional experiments are required to clearly define the mechanism(s) and fidelity of repair of 4 that may be different for either intra-or inter-strand cross-links, if the two possible LMDS are produced in cellular DNA.…”

Section: Discussionmentioning

confidence: 78%

Oxidation of the sugar moiety of DNA by ionizing radiation or bleomycin could induce the formation of a cluster DNA lesion

Regulus¹,

Duroux²,

Bayle

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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147

161

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Bleomycin, a radiomimetic drug currently used in human cancer therapy, is a well known carcinogen. Its toxicity is mostly attributed to its potentiality to induce DNA double strand breaks likely arising from the formation of two vicinal DNA strand breaks, initiated by C4-hydrogen abstraction on the 2-deoxyribose moiety.In this work we demonstrate that such a hydrogen abstraction reaction is able to induce the formation of a clustered DNA lesion, involving a 3 strand break together with a modified sugar residue exhibiting a reactive ␣,␤-unsaturated aldehyde that further reacts with a proximate cytosine base. The lesion thus produced was detected as a mixture of four isomers by HPLC coupled to tandem mass spectrometry subsequent to DNA extraction and enzymatic digestion. The modified nucleosides that constitute new types of cytosine adducts were identified as the likely two pairs of diastereomers of 6-(2-deoxy-␤-Derythro-pentofuranosyl)-2-hydroxy-3(3-hydroxy-2-oxopropyl)-2,6-dihydroimidazo[1,2-c]-pyrimidin-5(3H)-one as inferred from mass spectrometry and NMR analyses of the chemically synthesized nucleosides. We demonstrate that bleomycin, and to a minor extent ionizing radiation, are able to induce significant amounts of the cytosine damage in cellular DNA. In addition, the repair kinetic of the lesion in a human lymphocyte cell line is rather slow, with a half-life of 10 h. The 2 -deoxycytidine adducts thus characterized that represent the first example of complex DNA lesions isolated and identified in cellular DNA upon one radical hit are likely to play an important role in the toxicity of bleomycin.cluster lesions ͉ DNA damage ͉ DNA repair

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“…11,12 These bulky DNA lesions can be repaired by the nucleotide excision repair (NER) system. 3,6 If not properly corrected, they are premutagenic by three conceivable models 6,11,[13][14][15][16] : (1) incorporation of T opposite the altered bases by DNA polymerases that treat them as if they were an adenine (A); (2) direct lesion bypass by an error-prone DNA polymerase that incorporates an A opposite a C within the pyrimidine dimer; and (3) deamination of C within the dimer, giving rise to T or the related uracil, followed by "correct" bypass during DNA replication. These errors may precede or occur during DNA replication, and cause C→T transitions (about 70%) or CC→TT tandem mutations (about 10%) that are termed "signature mutations" for UV(B) mutagenesis, namely they are specific to this mutagen.…”

Section: Direct Dna Damagementioning

confidence: 99%

“…18,19 Its genotoxic and cytotoxic actions are the result of photodynamic effects that are strongly oxygen-dependent (Figure 2). 6,[12][13][14]18 Once UVR is absorbed, mutagenic oxidative reactions between the excited chromophores and cellular DNA may be triggered via two main mechanisms 6,[12][13][14]18 : In type I photosensitized reactions the energy is directly transferred to DNA, whereas in type II photosensitized reactions the energy is transferred to molecular oxygen, with DNA damage occurring via ensuing reactive oxygen species (ROS).…”

Section: Direct Dna Damagementioning

confidence: 99%

The dark side of the light: mechanisms of photocarcinogenesis

Coelho

Matos

Apetato

2016

Clinics in Dermatology

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Ultraviolet radiation (UVR) can have a beneficial biologic impact on skin, but it is also the most significant environmental risk factor for skin cancer development. Photocarcinogenesis comprises a complex interplay between the carcinogenic UVR, skin, and the immune system. UVB is absorbed by the superficial skin layers and is mainly responsible for direct DNA damage, which, if unrepaired, can lead to mutations in key cancer genes. UVA is less carcinogenic, penetrates deeper in the dermis, and mainly causes indirect oxidative damage to cellular DNA, proteins, and lipids, via photosensitized reactions. UVR not only induces mutagenesis, altering proliferation and differentiation of skin cells, but also has several immunosuppressive effects that compromise tumor immunosurveillance by impairing antigen presentation, inducing suppressive cells, and modulating the cytokine environment. This review focuses upon molecular and cellular effects of UVR, regarding its role in skin cancer development.

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Repair of the three main types of bipyrimidine DNA photoproducts in human keratinocytes exposed to UVB and UVA radiations

Cited by 137 publications

References 52 publications

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

Oxidation of the sugar moiety of DNA by ionizing radiation or bleomycin could induce the formation of a cluster DNA lesion

The dark side of the light: mechanisms of photocarcinogenesis

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