Cited by 153DNA Repair MechanismsSkin Protection and AgingMelanoma and MAPK Pathways

Roles of UVA radiation and DNA damage responses in melanoma pathogenesis

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Khan, Aiman Q., Travers, Jeffrey B., Kemp, Michael G.·2018·Environmental and Molecular Mutagenesis

Abstract

The growing incidence of melanoma is a serious public health issue that merits a thorough understanding of potential causative risk factors, which includes exposure to ultraviolet radiation (UVR). Though UVR has been classified as a complete carcinogen and has long been recognized for its ability to damage genomic DNA through both direct and indirect means, the precise mechanisms by which the UVA and UVB components of UVR contribute to the pathogenesis of melanoma have not been clearly defined. In this review, we therefore highlight recent studies that have addressed roles for UVA radiation in the generation of DNA damage and in modulating the subsequent cellular responses to DNA damage in melanocytes, which are the cell type that gives rise to melanoma. Recent research suggests that UVA not only contributes to the direct formation of DNA lesions but also impairs the removal of UV photoproducts from genomic DNA through oxidation and damage to DNA repair proteins. Moreover, the melanocyte microenvironment within the epidermis of the skin is also expected to impact melanomagenesis, and we therefore discuss several paracrine signaling pathways that have been shown to impact the DNA damage response in UV‐irradiated melanocytes. Lastly, we examine how alterations to the immune microenvironment by UVA‐associated DNA damage responses may contribute to melanoma development. Thus, there appear to be multiple avenues by which UVA may elevate the risk of melanoma. Protective strategies against excess exposure to UVA wavelengths of light therefore have the potential to decrease the incidence of melanoma. Environ. Mol. Mutagen. 59:438–460, 2018. © 2018 Wiley Periodicals, Inc.

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  1. Brash DE 2015 UV signature mutations Photochem Photobiol 91 15 26 25354245 PMC4294947
  2. Garcia-Borron JC Abdel-Malek Z Jimenez-Cervantes C 2014 MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation Pigment Cell Melanoma Res 27 699 720 24807163 PMC4150834

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Authors
Khan, A. Q., Travers, J. B., & Kemp, M. G.
Affiliations
Wright State University (US)
Corresponding author
Kemp, Michael G.
Venue
Environmental and Molecular Mutagenesis
Publisher
Wiley
Published
2018-02-21
Volume
59
Issue
5
Pages
438-460
ISSN
  • 0893-6692 (ISSN-L)
  • 1098-2280
OpenAlex
W2792144160
Cited by
152
References
321
Citations by year
2026: 10 · 2025: 20 · 2024: 25 · 2023: 22 · 2022: 20 · 2021: 23 · 2020: 20 · 2019: 7 · 2018: 5
FWCI
1.37
Type
journal article
Language
en
Open access
Locations
  • Environmental and Molecular Mutagenesis (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (AG048946)
  • National Institute of Environmental Health Sciences (ES020866)
  • U.S. Department of Veterans Affairs (1101CX000809)
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 › Molecular Biology › Melanoma and MAPK Pathways
Keywords
melanoma, UVA, UV-B radiation, DNA damage response, melanocytes, UV photoproducts, DNA repair proteins, oxidative DNA damage, paracrine signaling, tumor immune microenvironment, melanomagenesis
MeSH terms
DNA Damage, DNA Repair, Humans, Melanocytes, Melanoma, Neoplasms, Radiation-Induced, Skin, Skin Neoplasms, Ultraviolet Rays, Signal Transduction

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