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- Title
New functions of XPC in the protection of human skin cells from oxidative damage.
- Authors
D'Errico, Mariarosaria; Parlanti, Eleonora; Teson, Massimo; de Jesus, Bruno M Bernardes; Degan, Paolo; Calcagnile, Angelo; Jaruga, Pawel; Bjørås, Magnar; Crescenzi, Marco; Pedrini, Antonia M; Egly, Jean-Marc; Zambruno, Giovanna; Stefanini, Miria; Dizdaroglu, Miral; Dogliotti, Eugenia
- 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.
- Publication
The EMBO journal, 2006, Vol 25, Issue 18, p4305
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7601277