title: Repair of oxidatively generated DNA damage in Cockayne syndrome.
abstract: Defects in the repair of endogenously (especially oxidatively) generated DNA modifications and the resulting genetic instability can potentially explain the clinical symptoms of Cockayne syndrome (CS), a hereditary disease characterized by developmental defects and neurological degeneration. In this review, we describe the evidence for the involvement of CSA and CSB proteins, which are mutated in most of the CS patients, in the repair and processing of DNA damage induced by reactive oxygen species and the implications for the induction of cell death and mutations. Taken together, the data demonstrate that CSA and CSB, in addition to their established role in transcription-coupled nucleotide excision repair, can modulate the base excision repair (BER) of oxidized DNA bases both directly (by interaction with BER proteins) and indirectly (by modulating the expression of the DNA repair genes). Both nuclear and mitochondrial DNA repair is affected by mutations in CSA and CSB genes. However, the observed retardations of repair and the resulting accumulation of unrepaired endogenously generated DNA lesions are often mild, thus pointing to the relevance of additional roles of the CS proteins, e.g. in the mitochondrial response to oxidatively generated DNA damage and in the maintenance of gene transcription.
authors.affiliation: Institute of Pharmacy and Biochemistry, University of Mainz, Staudingerweg 5, D-55099 Mainz, Germany. khobta@uni-mainz.de
authors.forename: Andriy
authors.initials: A
authors.lastname: Khobta
authors.forename: Bernd
authors.initials: B
authors.lastname: Epe
mesh_terms: D000818:Animals; D003057:Cockayne Syndrome / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D010084:Oxidation-Reduction; D000075223:Poly-ADP-Ribose Binding Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C095472:ERCC8 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D014157:Transcription Factors; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes