Direct participation of DNA in the formation of singlet oxygen and base damage under UVA irradiation

Keratinocytes and melanocytes, two cutaneous cell types located within the epidermis, are the origin of most skin cancers, namely carcinomas and melanomas. These two types of tumors differ in many ways. First, carcinomas are almost 10 times more frequent than melanomas. In addition, the affected cellular pathways, the mutated genes and the metastatic properties of the tumors are not the same. This review addresses another specificity of melanomas: the role of photo‐oxidative stress. UVA efficiently produces reactive oxygen species in melanocytes, which results in more frequent oxidatively generated DNA lesions than in other cell types. The question of the respective contribution of UVB‐induced pyrimidine dimers and UVA‐mediated oxidatively generated lesions to mutagenesis in melanoma remains open. Recent results based on next‐generation sequencing techniques strongly suggest that the mutational signature associated with pyrimidine dimers is overwhelming in melanomas like in skin carcinomas. UVA‐induced oxidative stress may yet be indirectly linked to the genotoxic pathways involved in melanoma through its ability to hamper DNA repair activities.

Section: Uv-induced Dna Damage In Melanocytesmentioning

confidence: 99%

Oxidative Stress and Genotoxicity in Melanoma Induction: Impact on Repair Rather Than Formation of DNA Damage?

Douki

2020

“…The absorption of UV photons can induce different types of damage in the DNA molecule. The direct excitation of DNA by UVB wavelengths from sunlight (280–315 nm) results in photochemical reactions between adjacent pyrimidines, and the main products are cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6‐4) pyrimidone photoproducts (6‐4PPs) (5,6). Further irradiation with UVA wavelengths (315–400 nm) converts 6‐4PPs into their Dewar valence isomers (DewarPPs) (5,7).…”

Section: Introductionmentioning

confidence: 99%

DNA Damage Induced by Late Spring Sunlight in Antarctica

Fuentes-León

Oliveira

Ruiz

et al. 2020

Self Cite

Sunlight ultraviolet (UV) radiation constitutes an important environmental genotoxic agent that organisms are exposed to, as it can damage DNA directly, generating pyrimidine dimers, and indirectly, generating oxidized bases and single‐strand breaks (SSBs). These lesions can lead to mutations, triggering skin and eye disorders, including carcinogenesis and photoaging. Stratospheric ozone layer depletion, particularly in the Antarctic continent, predicts an uncertain scenario of UV incidence on the Earth in the next decades. This research evaluates the DNA damage caused by environmental exposure to late spring sunlight in the Antarctic Peninsula, where the ozone layer hole is more pronounced. These experiments were performed at the Brazilian Comandante Ferraz Antarctic Station, at King’s George Island, South Shetlands Islands. For comparison, tropical regions were also analyzed. Samples of plasmid DNA were exposed to sunlight. Cyclobutane pyrimidine dimers (CPDs), oxidized base damage and SSBs were detected using specific enzymes. In addition, an immunological approach was used to detect CPDs. The results reveal high levels of DNA damage induced by exposure under the Antarctic sunlight, inversely correlated with ozone layer thickness, confirming the high impact of ozone layer depletion on the DNA damaging action of sunlight in Antarctica.

“…Thus, those reaching the surface are predominantly UVA (95%) and UVB (5%), both apt to causing damage and inducing mutagenesis (5)(6)(7). UVA light may cause DNA damage through direct absorption of photons by nitrogenous bases, thereby giving rise to pyrimidine dimers, such as cyclobutane pyrimidine (CPD), pyrimidine and pyrimidone (6-4 PP) (8)(9)(10)(11)(12)(13)(14)(15). Moreover, it might also be detrimental through indirect mechanisms, such as photosensitization (7,16), or by late induction of the redox process associated to cellular metabolism (17,18), both leading to DNA and protein oxidation (14,19,20).…”

Section: Introductionmentioning

confidence: 99%

ATR/Chk1 Pathway is Activated by Oxidative Stress in Response to UVA Light in Human Xeroderma Pigmentosum Variant Cells

Moreno

García

Rocha

et al. 2018

Self Cite

The crucial role of DNA polymerase eta in protecting against sunlight‐induced tumors is evidenced in Xeroderma Pigmentosum Variant (XP‐V) patients, who carry mutations in this protein and present increased frequency of skin cancer. XP‐V cellular phenotypes may be aggravated if proteins of DNA damage response (DDR) pathway are blocked, as widely demonstrated by experiments with UVC light and caffeine. However, little is known about the participation of DDR in XP‐V cells exposed to UVA light, the wavelengths patients are mostly exposed. Here, we demonstrate the participation of ATR kinase in protecting XP‐V cells after receiving low UVA doses using a specific inhibitor, with a remarkable increase in sensitivity and γH2AX signaling. Corroborating ATR participation in UVA‐DDR, a significant increase in Chk1 protein phosphorylation, as well as S‐phase cell cycle arrest, is also observed. Moreover, the participation of oxidative stress is supported by the antioxidant action of N‐acetylcysteine (NAC), which significantly protects XP‐V cells from UVA light, even in the presence of the ATR inhibitor. These findings indicate that the ATR/Chk1 pathway is activated to control UVA‐induced oxidatively generated DNA damage and emphasizes the role of ATR kinase as a mediator of genomic stability in pol eta defective cells.