title: XPC deficiency is related to APE1 and OGG1 expression and function.
abstract: Oxidative DNA damage is considered to be a major cause of neurodegeneration and internal tumors observed in syndromes that result from nucleotide excision repair (NER) deficiencies, such as Xeroderma Pigmentosum (XP) and Cockayne Syndrome (CS). Recent evidence has shown that NER aids in removing oxidized DNA damage and may interact with base excision repair (BER) enzymes. Here, we investigated APE1 and OGG1 expression, localization and activity after oxidative stress in XPC-deficient cells. The endogenous APE1 and OGG1 mRNA levels were lower in XPC-deficient fibroblasts. However, XPC-deficient cells did not show hypersensitivity to oxidative stress compared with NER-proficient cells. To confirm the impact of an XPC deficiency in regulating APE1 and OGG1 expression and activity, we established an XPC-complemented cell line. Although the XPC complementation was only partial and transient, the transfected cells exhibited greater OGG1 expression and activity compared with XPC-deficient cells. However, the APE1 expression and activity did not significantly change. Furthermore, we observed a physical interaction between the XPC and APE1 proteins. Together, the results indicate that the responses of XPC-deficient cells under oxidative stress may not only be associated with NER deficiency per se but may also include new XPC functions in regulating BER proteins.
authors.affiliation: Laboratório de Biologia Molecular e Genômica, Departamento de Biologia Celular e Genética, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Julliane Tamara Araújo
authors.initials: JT
authors.lastname: de Melo
authors.affiliation: Laboratório de Biologia Molecular e Genômica, Departamento de Biologia Celular e Genética, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Ana Rafaela
authors.initials: AR
authors.lastname: de Souza Timoteo
authors.affiliation: Laboratório de Biologia Molecular e Genômica, Departamento de Biologia Celular e Genética, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Tirzah Braz Petta
authors.initials: TB
authors.lastname: Lajus
authors.affiliation: Laboratório de Biologia Molecular e Genômica, Departamento de Biologia Celular e Genética, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Juliana Alves
authors.initials: JA
authors.lastname: Brandão
authors.affiliation: Laboratório de Genética Mitocondrial, Departamento de Química, Instituto de Química, Universidade de São Paulo-USP, São Paulo, Brazil.
authors.forename: Nadja Cristhina
authors.initials: NC
authors.lastname: de Souza-Pinto
authors.affiliation: Laboratório de Reparo de DNA, Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo-USP, São Paulo, Brazil.
authors.forename: Carlos Frederico Martins
authors.initials: CF
authors.lastname: Menck
authors.affiliation: CEA, Institut de Radiobiologie Cellulaire et Moléculaire, 18 Route du Panorama, F-92265 Fontenay aux Roses, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Campalans
authors.affiliation: CEA, Institut de Radiobiologie Cellulaire et Moléculaire, 18 Route du Panorama, F-92265 Fontenay aux Roses, France.
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Radicella
authors.affiliation: Laboratório de Reparo de DNA, Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo-USP, São Paulo, Brazil; Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, CA, USA.
authors.forename: Alexandre Teixeira
authors.initials: AT
authors.lastname: Vessoni
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, CA, USA.
authors.forename: Alysson Renato
authors.initials: AR
authors.lastname: Muotri
authors.affiliation: Laboratório de Biologia Molecular e Genômica, Departamento de Biologia Celular e Genética, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil. Electronic address: lfagnez@ufrnet.br.
authors.forename: Lucymara Fassarella
authors.initials: LF
authors.lastname: Agnez-Lima
mesh_terms: D002478:Cells, Cultured; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047468:Immunoprecipitation; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D016877:Oxidants; D012333:RNA, Messenger; C086984:XPC protein, human; D006861:Hydrogen Peroxide; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: APE1; DNA damage; DNA repair; OGG1; Oxidative stress; XPC