title: Mitochondrial repair of 8-oxoguanine is deficient in Cockayne syndrome group B.
abstract: Reactive oxygen species, which are prevalent in mitochondria, cause oxidative DNA damage including the mutagenic DNA lesion 7,8-dihydroxyguanine (8-oxoG). Oxidative damage to mitochondrial DNA has been implicated as a causative factor in a wide variety of degenerative diseases, and in cancer and aging. 8-oxoG is repaired efficiently in mammalian mitochondrial DNA by enzymes in the base excision repair pathway, including the 8-oxoguanine glycosylase (OGG1), which incizes the lesion in the first step of repair. Cockayne syndrome (CS) is a segmental premature aging syndrome in humans that has two complementation groups, CSA and CSB. Previous studies showed that CSB-deficient cells have reduced capacity to repair 8-oxoG. This study examines the role of the CSB gene in regulating repair of 8-oxoG in mitochondrial DNA in human and mouse cells. 8-oxoG repair was measured in liver cells from CSB deficient mice and in human CS-B cells carrying expression vectors for wild type or mutant forms of the human CSB gene. For the first time we report that CSB stimulates repair of 8-oxoG in mammalian mitochondrial DNA. Furthermore, evidence is presented to support the hypothesis that wild type CSB regulates expression of OGG1.
authors.affiliation: Danish Center for Molecular Gerontology, Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus C, Denmark.
authors.forename: Tinna
authors.initials: T
authors.lastname: Stevnsner
authors.forename: Simon
authors.initials: S
authors.lastname: Nyaga
authors.forename: Nadja C
authors.initials: NC
authors.lastname: de Souza-Pinto
authors.forename: Gijsbertus T J
authors.initials: GT
authors.lastname: van der Horst
authors.forename: Theo G M F
authors.initials: TG
authors.lastname: Gorgels
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hogue
authors.forename: Tina
authors.initials: T
authors.lastname: Thorslund
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D003057:Cockayne Syndrome / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics; D017931:DNA Primers; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004272:DNA, Mitochondrial / Q000235:genetics*; D043382:DNA-Formamidopyrimidine Glycosylase; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial; D000075223:Poly-ADP-Ribose Binding Proteins; C024829:8-hydroxyguanine; D006147:Guanine; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D004265:DNA Helicases; C078673:ERCC6 protein, human; C513075:Ercc6 protein, mouse; D045643:DNA Repair Enzymes