title: The transcriptional response after oxidative stress is defective in Cockayne syndrome group B cells.
abstract: Cockayne syndrome (CS) is a human hereditary disease belonging to the group of segmental progerias, and the clinical phenotype is characterized by postnatal growth failure, neurological dysfunction, cachetic dwarfism, photosensitivity, sensorineural hearing loss, and retinal degradation. CS-B cells are defective in transcription-coupled DNA repair, base excision repair, transcription, and chromatin structural organization. Using array analysis, we have examined the expression profile in CS complementation group B (CS-B) fibroblasts after exposure to oxidative stress (H2O2) before and after complete complementation with the CSB gene. The following isogenic cell lines were compared: CS-B cells (CS-B null), CS-B cells complemented with wild-type CSB (CS-B wt), and a stably transformed cell line with a point mutation in the ATPase domain of CSB (CS-B ATPase mutant). In the wt rescued cells, we detected significant induction (two-fold) of 112 genes out of the 6912 analysed. The patterns suggested an induction or upregulation of genes involved in several DNA metabolic processes including DNA repair, transcription, and signal transduction. In both CS-B mutant cell lines, we found a general deficiency in transcription after oxidative stress, suggesting that the CSB protein influenced the regulation of transcription of certain genes. Of the 6912 genes, 122 were differentially regulated by more than two-fold. Evidently, the ATPase function of CSB is biologically important as the deficiencies seen in the ATPase mutant cells are very similar to those observed in the CS-B-null cells. Some major defects are in the transcription of genes involved in DNA repair, signal transduction, and ribosomal functions.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, 5600 Nathan Schock Drive, National Institute of Health, Baltimore, MD 21224, USA.
authors.forename: Kasper J
authors.initials: KJ
authors.lastname: Kyng
authors.forename: Alfred
authors.initials: A
authors.lastname: May
authors.forename: Robert M
authors.initials: RM
authors.lastname: Brosh
authors.forename: Wen-Hsing
authors.initials: WH
authors.lastname: Cheng
authors.forename: Catheryne
authors.initials: C
authors.lastname: Chen
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015152:Blotting, Northern; D002460:Cell Line / Q000187:drug effects / Q000201:enzymology; D002461:Cell Line, Transformed; D003057:Cockayne Syndrome / Q000201:enzymology / Q000473:pathology*; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D045643:DNA Repair Enzymes; D004261:DNA Replication / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005816:Genetic Complementation Test; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D011993:Recombinant Fusion Proteins; D006861:Hydrogen Peroxide; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes