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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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“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]
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“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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Melis, J. P. M., Kuiper, R., Zwart, E. P., Robinson, J. E., Pennings, J., van Oostrom, C. V., Luijten, M., & van Steeg, H. (2013) · DNA Repair · doi:10.1016/j.dnarep.2013.08.019 · Cited by 44
DNA repair triggered by sensors of helical dynamics
Maillard, O., Camenisch, U., Clement, F. C., Blagoev, K. B., & Naegeli, H. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.08.008 · Cited by 45
Mitochondria and oxygen homeostasis
Mori, M. P., Penjweini, R., Knutson, J. R., Wang, P., & Hwang, P. M. (2021) · FEBS Journal · doi:10.1111/febs.16115 · Cited by 46
Measurement of oxidatively generated base damage in cellular DNA and urine
Cadet, J., & Poulsen, H. E. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.03.004 · Cited by 44
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Premature Skin Aging Features Rescued by Inhibition of NADPH Oxidase Activity in XPC-Deficient Mice
Hosseini, M., Mahfouf, W., Serrano-Sanchez, M., Raad, H., Harfouche, G., Bonneu, M., Claverol, S., Mazurier, F., Rossignol, R., Taieb, A., et al. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2014.511 · Cited by 42
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A microarray to measure repair of damaged plasmids by cell lysates
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Nucleotide excision repair activity on DNA damage induced by photoactivated methylene blue
Berra, C. M., de Oliveira, C. S., Garcia, C. C. M., Rocha, C. R. R., Lerner, L. K., Lima, L. C. D. A., Baptista, M. D. S., & Menck, C. F. M. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.03.026 · Cited by 40
Measurement of oxidatively generated base damage to nucleic acids in cells: facts and artifacts
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Independent Generation of C5‘-Nucleosidyl Radicals in Thymidine and 2‘-Deoxyguanosine
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Metadata
- 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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