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  • The EMBO Journal (2006) 25, 4305 - 4315
  • doi:10.1038/sj.emboj.7601277

Published online: 7 September 2006

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

Mariarosaria D'Errico1, Eleonora Parlanti1,a, Massimo Teson2,a, Bruno M Bernardes de Jesus3,a, Paolo Degan4, Angelo Calcagnile1, Pawel Jaruga5,6, Magnar Bjørås7, Marco Crescenzi1, Antonia M Pedrini8, Jean-Marc Egly3, Giovanna Zambruno2, Miria Stefanini8, Miral Dizdaroglu6 and Eugenia Dogliotti1

  1. Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy
  2. Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy
  3. Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM, Illkirch, CU, Strasbourg, France
  4. Istituto Nazionale per la Ricerca sul Cancro, Department of Translational Oncology, Genova, Italy
  5. Chemical and Biochemical Engineering Department, University of Maryland Baltimore County, Baltimore, MD, USA
  6. Chemical Science and Technology Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, USA
  7. Department of Molecular Biology, Institute of Medical Microbiology and Centre of Molecular Biology and Neuroscience, University of Oslo, Rikshospitalet Radiumhospitalet HF, Oslo, Norway
  8. Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, Italy

Correspondence to:

Eugenia Dogliotti, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Tel.:+39 06 4990 2580; Fax: +39 06 4990 3650; E-mail: dogliott@iss.it

aThese authors contributed equally to this work

Received 6 February 2006; Accepted 12 July 2006

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.

  • Keywords:

    • cancer,
    • DNA repair,
    • keratinocytes,
    • oxidative DNA damage,
    • xeroderma pigmentosum