Cited by 86DNA Repair MechanismsSkin Protection and AgingEffects of Radiation Exposure

Oxidative stress-induced protein damage inhibits DNA repair and determines mutation risk and therapeutic efficacy

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McAdam, Elizabeth, Brem, Reto, Karran, Peter·2016·Molecular Cancer Research

Published version of a preprint

Abstract

The relationship between sun exposure and nonmelanoma skin cancer risk is well established. Solar UV (wavelength 280–400 nm) is firmly implicated in skin cancer development. Nucleotide excision repair (NER) protects against cancer by removing potentially mutagenic DNA lesions induced by UVB (280–320 nm). How the 20-fold more abundant UVA (320–400 nm) component of solar UV radiation increases skin cancer risk is not understood. Here it is demonstrated that the contribution of UVA to the effect of UV radiation on cultured human cells is largely independent of its ability to damage DNA. Instead, the effects of UVA reflect the induction of oxidative stress that causes extensive protein oxidation. Because NER proteins are among those damaged, UVA irradiation inhibits NER and increases the susceptibility of the cells to mutation by UVB. NER inhibition is a common consequence of oxidative stress. Exposure to chemical oxidants, treatment with drugs that deplete cellular antioxidants, and interventions that interfere with glucose metabolism to disrupt the supply of cellular reducing power all inhibit NER. Tumor cells are often in a condition of oxidative stress and one effect of the NER inhibition that results from stress-induced protein oxidation is an increased sensitivity to the anticancer drug cisplatin. Implications: As NER is both a defense against cancer and a significant determinant of cell survival after treatment with anticancer drugs, its attenuation by protein damage under conditions of oxidative stress has implications for both cancer risk and for the effectiveness of anticancer therapy. Mol Cancer Res; 14(7); 612–22. ©2016 AACR.

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  • The susceptibility of NER proteins to oxidation generated by UVA or other substances compromises cell protection against DNA damage, with implications for carcinogenesis.

    “The susceptibility of the NER proteins to the oxidation generated by UVA or other substances compromises the cell protection against DNA damage, which has clear implications for carcinogenesis [264].”

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Authors
McAdam, E., Brem, R., & Karran, P.
Affiliations
The Francis Crick Institute (GB)
Corresponding author
Karran, Peter
Venue
Molecular Cancer Research
Published
2016-07-01
Volume
14
Issue
7
Pages
612-622
ISSN
  • 1541-7786 (ISSN-L)
  • 1557-3125
OpenAlex
W2341278327
Cited by
86
References
50
Citations by year
2026: 2 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 10 · 2021: 13 · 2020: 13 · 2019: 9 · 2018: 6 · 2017: 6 · 2016: 7
FWCI
4.85
Type
journal article
Language
en
Open access
Locations
  • Molecular Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • Francis Crick Institute (10098)
  • Cancer Research UK (A3558, 11584, A11584)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords
oxidative stress, protein oxidation, nucleotide excision repair, UVA, UV-B radiation, non-melanoma skin cancer, DNA repair inhibition, cisplatin sensitivity, reducing power, glucose metabolism, anticancer drug efficacy
MeSH terms
DNA Damage, DNA Repair, HeLa Cells, Humans, Mutation, Risk Factors, Ultraviolet Rays, Keratinocytes, Mutagenesis, Reactive Oxygen Species, Oxidative Stress, Cell Line, Tumor

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