Mitochondrial repair of 8-oxguanine is deficient in Cockayne syndrome group B

• Published in: Oncogene Vol. 21; no. 57; pp. 8675 - 8682
• Main Authors: Stevnsner, T, Nyaga, S, de Souza-Pinto, NC, van der Horst, GTJ, Gorgels, TGMF, Hogue, BA, Thorslund, T, Bohr, V A
• Format: Journal Article
• Language: English
• Published: 12-12-2002
• ISSN: 0950-9232
• DOI: 10.1038/sj.onc.1205994

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.