New functions of XPC in the protection of human skin cells from oxidative damage
Open accessAbstract
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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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].”
From Sunlight damage to cellular DNA: focus on oxidatively generated lesions (2017) · cites this paper as [244]
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]”
From Sunlight damage to cellular DNA: focus on oxidatively generated lesions (2017) · cites this paper as [244]
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DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood
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Dissection of the Molecular Defects Caused by Pathogenic Mutations in the DNA Repair Factor XPC
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On the relevance of hydroxyl radical to purine DNA damage
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Measurement of oxidatively induced DNA damage and its repair, by mass spectrometric techniques
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Xeroderma pigmentosum genes: Functions inside and outside DNA repair
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A quantitative assay for assessing the effects of DNA lesions on transcription
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Role of Nicotinamide in Genomic Stability and Skin Cancer Chemoprevention
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DNA repair as a human biomonitoring tool: Comet assay approaches
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The Pattern of Signatures in Gastric Cancer Prognosis
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The role of XPC: Implications in cancer and oxidative DNA damage
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The role of glutathione in the regulation of nucleotide excision repair during oxidative stress
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Self-citationMouse Models for Xeroderma Pigmentosum Group A and Group C Show Divergent Cancer Phenotypes
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Nucleotide Excision Repair: From Molecular Defects to Neurological Abnormalities
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Cell-Autonomous Progeroid Changes in Conditional Mouse Models for Repair Endonuclease XPG Deficiency
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Role of XPD in cellular functions: To TFIIH and beyond
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The Fate of C5′ Radicals of Purine Nucleosides under Oxidative Conditions
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Role of nucleotide excision repair proteins in oxidative DNA damage repair: an updating
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Self-citationThe cross talk between pathways in the repair of 8-oxo-7,8-dihydroguanine in mouse and human cells
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High frequency of the V548A fs X572 XPC mutation in Tunisia: implication for molecular diagnosis
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Oxidative DNA damage in polymorphonuclear leukocytes of patients with familial Mediterranean fever
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The effect of oxidative stress on nucleotide-excision repair in colon tissue of newborn piglets
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Slow accumulation of mutations in Xpc−/− mice upon induction of oxidative stress
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DNA repair triggered by sensors of helical dynamics
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Mitochondria and oxygen homeostasis
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Measurement of oxidatively generated base damage in cellular DNA and urine
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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)
- ORCID
- Venue
- The EMBO Journal
- Published
- 2006-09-07
- Volume
- 25
- Issue
- 18
- Pages
- 4305-4315
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1570445
- 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
- bronze
- doi.org
- Licence
- 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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