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

Oncogene. 2002 Dec 12;21(57):8675-82. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line, Transformed
  • Cockayne Syndrome / genetics*
  • DNA Helicases / genetics
  • DNA Primers
  • DNA Repair Enzymes
  • DNA Repair*
  • DNA, Mitochondrial / genetics*
  • DNA-Formamidopyrimidine Glycosylase
  • Guanine / analogs & derivatives*
  • Guanine / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • N-Glycosyl Hydrolases / metabolism
  • Poly-ADP-Ribose Binding Proteins


  • DNA Primers
  • DNA, Mitochondrial
  • Poly-ADP-Ribose Binding Proteins
  • 8-hydroxyguanine
  • Guanine
  • N-Glycosyl Hydrolases
  • DNA-Formamidopyrimidine Glycosylase
  • DNA Helicases
  • ERCC6 protein, human
  • Ercc6 protein, mouse
  • DNA Repair Enzymes