PMID- 16957781 OWN - NLM STAT- MEDLINE DCOM- 20061024 LR - 20231105 IS - 0261-4189 (Print) IS - 1460-2075 (Electronic) IS - 0261-4189 (Linking) VI - 25 IP - 18 DP - 2006 Sep 20 TI - New functions of XPC in the protection of human skin cells from oxidative damage. PG - 4305-15 AB - 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. FAU - D'Errico, Mariarosaria AU - D'Errico M AD - Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Rome, Italy. FAU - Parlanti, Eleonora AU - Parlanti E FAU - Teson, Massimo AU - Teson M FAU - de Jesus, Bruno M Bernardes AU - de Jesus BM FAU - Degan, Paolo AU - Degan P FAU - Calcagnile, Angelo AU - Calcagnile A FAU - Jaruga, Pawel AU - Jaruga P FAU - Bjoras, Magnar AU - Bjoras M FAU - Crescenzi, Marco AU - Crescenzi M FAU - Pedrini, Antonia M AU - Pedrini AM FAU - Egly, Jean-Marc AU - Egly JM FAU - Zambruno, Giovanna AU - Zambruno G FAU - Stefanini, Miria AU - Stefanini M FAU - Dizdaroglu, Miral AU - Dizdaroglu M FAU - Dogliotti, Eugenia AU - Dogliotti E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060907 PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (Bromates) RN - 0 (DNA-Binding Proteins) RN - 0 (Oxidants) RN - 04MB35W6ZA (potassium bromate) RN - 156533-33-4 (RAD23A protein, human) RN - 156533-34-5 (XPC protein, human) RN - 5614-64-2 (8-hydroxyguanine) RN - 5Z93L87A1R (Guanine) RN - EC 3.2.2.- (DNA Glycosylases) RN - EC 3.2.2.- (oxoguanine glycosylase 1, human) RN - EC 6.5.1.- (DNA Repair Enzymes) SB - IM MH - Bromates/toxicity MH - Cells, Cultured MH - *DNA Damage MH - DNA Glycosylases/metabolism MH - DNA Repair MH - DNA Repair Enzymes MH - DNA-Binding Proteins/deficiency/genetics/*metabolism MH - Guanine/analogs & derivatives/metabolism MH - Humans MH - Keratinocytes/drug effects/*metabolism/radiation effects MH - Oxidants/toxicity MH - Skin Neoplasms/etiology MH - X-Rays MH - Xeroderma Pigmentosum/complications/genetics/metabolism PMC - PMC1570445 EDAT- 2006/09/08 09:00 MHDA- 2006/10/25 09:00 PMCR- 2007/09/20 CRDT- 2006/09/08 09:00 PHST- 2006/02/06 00:00 [received] PHST- 2006/07/12 00:00 [accepted] PHST- 2006/09/08 09:00 [pubmed] PHST- 2006/10/25 09:00 [medline] PHST- 2006/09/08 09:00 [entrez] PHST- 2007/09/20 00:00 [pmc-release] AID - 7601277 [pii] AID - 10.1038/sj.emboj.7601277 [doi] PST - ppublish SO - EMBO J. 2006 Sep 20;25(18):4305-15. doi: 10.1038/sj.emboj.7601277. Epub 2006 Sep 7.