Cited by 271DNA Repair MechanismsCarcinogens and Genotoxicity AssessmentDNA and Nucleic Acid Chemistry

New functions of XPC in the protection of human skin cells from oxidative damage

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D'Errico, Mariarosaria, Parlanti, Eleonora, Teson, Massimo, de Jesus, Bruno M Bernardes, Degan, Paolo, Calcagnile, Angelo, Jaruga, Pawel, Bjørås, Magnar +7 more·2006·The EMBO Journal

Abstract

Xeroderma pigmentosum (XP) C is involved in the recognition of a variety of bulky DNA-distorting lesions in nucleotide excision repair. Here, we show that XPC plays an unexpected and multifaceted role in cell protection from oxidative DNA damage. XP-C primary keratinocytes and fibroblasts are hypersensitive to the killing effects of DNA-oxidizing agents and this effect is reverted by expression of wild-type XPC. Upon oxidant exposure, XP-C primary keratinocytes and fibroblasts accumulate 8,5'-cyclopurine 2'-deoxynucleosides in their DNA, indicating that XPC is involved in their removal. In the absence of XPC, a decrease in the repair rate of 8-hydroxyguanine (8-OH-Gua) is also observed. We demonstrate that XPC-HR23B complex acts as cofactor in base excision repair of 8-OH-Gua, by stimulating the activity of its specific DNA glycosylase OGG1. In vitro experiments suggest that the mechanism involved is a combination of increased loading and turnover of OGG1 by XPC-HR23B complex. The accumulation of endogenous oxidative DNA damage might contribute to increased skin cancer risk and account for internal cancers reported for XP-C patients.

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Crossref · 10.1038/sj.emboj.7601277

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  • Studies using human keratinocytes and fibroblasts from XPC patients showed that XPC is important to prevent accumulation of oxidatively generated DNA damage and its killing effects after exposure to oxidants such as potassium bromate, X-rays, and methylene blue plus visible light.

    “Additionally, studies using human keratinocytes and fibroblasts from XPC patients showed that this protein is important to prevent the accumulation of oxidatively generated DNA damage and its killing effects after exposure to oxidants, such as potassium bromate, X-rays, and methylene blue plus visible light [244,245,253].”
  • XPC can functionally interact with several BER proteins, including 3-methyladenine DNA glycosylase, TDG, UDG, APE1, and OGG1.

    “In addition to the main role of the XPC complex in the recognition of DNA-distorting lesions, it has been demonstrated that it can functionally interact with several BER proteins, including 3-methyladenine DNA glycosylase, thymine DNA glycosylase (TDG), uracil-DNA glycosylases (UDG), apurinic/apyrimidinic endonuclease 1 (APE1), and 8-oxoguanine DNA glycosylase (OGG1) [244][245][246][247][248][249]”

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Authors
D'Errico, M., Parlanti, E., Teson, M., de Jesus, B. M. B., Degan, P., Calcagnile, A., Jaruga, P., Bjørås, M., Crescenzi, M., Pedrini, A. M., Egly, J., Zambruno, G., Stefanini, M., Dizdaroglu, M., & Dogliotti, E.
Affiliations
  • Istituto Superiore di Sanità (IT)
  • Istituto Dermopatico dell'Immacolata (IT)
  • University of Oslo (NO)
  • Istituto di Genetica Molecolare (IT)
  • Centre National de la Recherche Scientifique (FR)
Venue
The EMBO Journal
Published
2006-09-07
Volume
25
Issue
18
Pages
4305-4315
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W2062150992
Cited by
271
References
51
Citations by year
2026: 5 · 2025: 10 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 19 · 2020: 9 · 2019: 14 · 2018: 9 · 2017: 6 · 2016: 12 · 2015: 13 · 2014: 14 · 2013: 15 · 2012: 24
FWCI
8.42
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • Fondazione Cariplo
  • Ministero della Salute
  • Ministero dell’Istruzione, dell’Università e della Ricerca
  • Associazione Italiana per la Ricerca sul Cancro
  • National Institute of Standards and Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
XPC, xeroderma pigmentosum group C, oxidative DNA damage, base excision repair, 8-oxoguanine, OGG1, keratinocytes, fibroblasts, skin cancer risk, DNA glycosylase
MeSH terms
Bromates, Cells, Cultured, DNA Damage, DNA Repair, DNA-Binding Proteins, Guanine, Humans, Skin Neoplasms, X-Rays, Xeroderma Pigmentosum, Keratinocytes, Oxidants, DNA Repair Enzymes, DNA Glycosylases

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