title: Impaired repair of ionizing radiation-induced DNA damage in Cockayne syndrome cells.
abstract: Cockayne syndrome (CS) cells are defective in transcription-coupled repair (TCR) and sensitive to oxidizing agents, including ionizing radiation. We examined the hypothesis that TCR plays a role in ionizing radiation-induced oxidative DNA damage repair or alternatively that CS plays a role in transcription elongation after irradiation. Irradiation with doses up to 100 Gy did not inhibit RNA polymerase II-dependent transcription in normal and CS-B fibroblasts. In contrast, RNA polymerase I-dependent transcription was severely inhibited at 5 Gy in normal cells, indicating different mechanisms of transcription response to X rays. The frequency of radiation-induced base damage was 2 × 10(-7) lesions/base/Gy, implying that 150 Gy is required to induce one lesion/30-kb transcription unit; no TCR of X-ray-induced base damage in the p53 gene was observed. Therefore, it is highly unlikely that defective TCR underlies the sensitivity of CS to ionizing radiation. Overall genome repair levels of radiation-induced DNA damage measured by repair replication were significantly reduced in CS-A and CS-B cells. Taken together, the results do not provide evidence for a key role of TCR in repair of radiation-induced oxidative damages in human cells; rather, impaired repair of oxidative lesions throughout the genome may contribute to the CS phenotype.
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2300 RC Leiden, The Netherlands.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cramers
authors.forename: Esther E
authors.initials: EE
authors.lastname: Verhoeven
authors.forename: A Ronald
authors.initials: AR
authors.lastname: Filon
authors.forename: Davy A P
authors.initials: DA
authors.lastname: Rockx
authors.forename: Susy J
authors.initials: SJ
authors.lastname: Santos
authors.forename: Anneke A
authors.initials: AA
authors.lastname: van der Leer
authors.forename: Jos C S
authors.initials: JC
authors.lastname: Kleinjans
authors.forename: Albert A
authors.initials: AA
authors.lastname: van Zeeland
authors.forename: Leon H F
authors.initials: LH
authors.lastname: Mullenders
mesh_terms: D002470:Cell Survival / Q000528:radiation effects*; D002478:Cells, Cultured; D003057:Cockayne Syndrome / Q000235:genetics* / Q000473:pathology*; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D011829:Radiation Dosage