No Formation of DNA Double-Strand Breaks and No Activation of Recombination Repair with UVA

Rizzo, Jennifer L.; Dunn, Jessica; Rees, Adam; Rünger, Thomas M.

doi:10.1038/jid.2010.365

Cited by 43 publications

(21 citation statements)

References 61 publications

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“…UVA was originally not expected to be involved in the generation of dsbs due to the relative low photonic energy. This idea was supported by a recent study of Rizzo et al (17) who did interpret their experimental data as being indicative for no dsbs induced in cells exposed towards UVA. Additionally, Cadet and Douki (10) argued that induction of dsbs via clustered ssbs is unlikely, since UVA induces more than twice as much 8-oxo-dG compared to ssbs or alkali labile sites.…”

Section: Introductionsupporting

confidence: 56%

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages

Greinert¹,

Volkmer²,

Henning³

et al. 2012

Nucleic Acids Research

113

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UVA (320–400 nm) represents the main spectral component of solar UV radiation, induces pre-mutagenic DNA lesions and is classified as Class I carcinogen. Recently, discussion arose whether UVA induces DNA double-strand breaks (dsbs). Only few reports link the induction of dsbs to UVA exposure and the underlying mechanisms are poorly understood. Using the Comet-assay and γH2AX as markers for dsb formation, we demonstrate the dose-dependent dsb induction by UVA in G1-synchronized human keratinocytes (HaCaT) and primary human skin fibroblasts. The number of γH2AX foci increases when a UVA dose is applied in fractions (split dose), with a 2-h recovery period between fractions. The presence of the anti-oxidant Naringin reduces dsb formation significantly. Using an FPG-modified Comet-assay as well as warm and cold repair incubation, we show that dsbs arise partially during repair of bi-stranded, oxidative, clustered DNA lesions. We also demonstrate that on stretched chromatin fibres, 8-oxo-G and abasic sites occur in clusters. This suggests a replication-independent formation of UVA-induced dsbs through clustered single-strand breaks via locally generated reactive oxygen species. Since UVA is the main component of solar UV exposure and is used for artificial UV exposure, our results shine new light on the aetiology of skin cancer.

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Section: Introductionsupporting

confidence: 56%

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages

Greinert¹,

Volkmer²,

Henning³

et al. 2012

Nucleic Acids Research

113

View full text Add to dashboard Cite

show abstract

“…It was shown using the comet assay and the alkaline elution analysis that UVA irradiation of cells gave rise to the formation of alkali-labile sites, mostly strand breaks. It was recently confirmed that UVA radiation, in contrast to earlier suggestions, is not able to generate double strand breaks (114).…”

Section: Uva-mediated Oxidatively Generated Dna Damage In Cellscontrasting

confidence: 41%

Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions^†

Cadet¹,

Mouret²,

Ravanat³

et al. 2012

Photochem & Photobiology

266

251

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The survey focuses on recent aspects of photochemical reactions to cellular DNA that are implicated through the predominant formation of mostly bipyrimidine photoproducts in deleterious effects of human exposure to sunlight. Recent developments in analytical methods have allowed accurate and quantitative measurements of the main DNA photoproducts in cells and human skin. Highly mutagenic CC and CT bipyrimidine photoproducts, including cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) are generated in low yields with respect to TT and TC photoproducts. Another striking finding deals with the formation of Dewar valence isomers, the third class of bipyrimidine photoproducts that is accounted for by UVA-mediated isomerization of initially UVB generated 6-4PPs. Cyclobutadithymine (T< >T) has been unambiguously shown to be involved in the genotoxicity of UVA radiation. Thus, T< >T is formed in UVA-irradiated cellular DNA according to a direct excitation mechanism with a higher efficiency than oxidatively generated DNA damage that arises mostly through the Type II photosensitization mechanism. C<>C and C< >T are repaired at rates intermediate between those of T< >T and 6-4TT. Evidence has been also provided for the occurrence of photosensitized reactions mediated by exogenous agents that act either in an independent way or through photodynamic effects.

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“…3c). To confirm that it was UVR-induced DNA damage present in keratinocytes that was blocked by skin-resident T cell supernatants, cultured keratinocyte monolayers were analyzed for γH2AX immunoreactivity (43) following UVR treatment (Fig. 6e).…”

Section: Resultsmentioning

confidence: 99%

Skin-Resident T Cells Sense Ultraviolet Radiation–Induced Injury and Contribute to DNA Repair

MacLeod

Rudolph

Corriden

et al. 2014

The Journal of Immunology

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Skin-resident T cells have been shown to play important roles in tissue homeostasis and wound repair, but their role in UV radiation (UVR)–mediated skin injury and subsequent tissue regeneration is less clear. In this study, we demonstrate that acute UVR rapidly activates skin-resident T cells in humans and dendritic epidermal γδ T cells (DETCs) in mice through mechanisms involving the release of ATP from keratinocytes. Following UVR, extracellular ATP leads to an increase in CD69 expression, proliferation, and IL-17 production, and to changes in DETC morphology. Furthermore, we find that the purinergic receptor P2X7 and caspase-1 are necessary for UVR-induced IL-1 production in keratinocytes, which increases IL-17 secretion by DETCs. IL-17, in turn, induces epidermal TNF-related weak inducer of apoptosis and growth arrest and DNA damage–associated gene 45, two molecules linked to the DNA repair response. Finally, we demonstrate that DETCs and human skin-resident T cells limit DNA damage in keratinocytes. Taken together, our findings establish a novel role for skin-resident T cells in the UVR-associated DNA repair response and underscore the importance of skin-resident T cells to overall skin regeneration.

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No Formation of DNA Double-Strand Breaks and No Activation of Recombination Repair with UVA

Cited by 43 publications

References 61 publications

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages

Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions^†

Skin-Resident T Cells Sense Ultraviolet Radiation–Induced Injury and Contribute to DNA Repair

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No Formation of DNA Double-Strand Breaks and No Activation of Recombination Repair with UVA

Cited by 43 publications

References 61 publications

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages

Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions†

Skin-Resident T Cells Sense Ultraviolet Radiation–Induced Injury and Contribute to DNA Repair

Contact Info

Product

Resources

About

Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions^†