Radiosensitivity in Nijmegen Breakage Syndrome cells is attributable to a repair defect and not cell cycle checkpoint defects
| Autor: | Pm, Girard, Nicolas Foray, Stumm M, Waugh A, Riballo E, Rs, Maser, Wp, Phillips, Petrini J, Cf, Arlett, Pa, Jeggo |
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| Rok vydání: | 2000 |
| Předmět: |
DNA Repair
Cell Survival Cell Cycle Mitosis Chromosome Breakage DNA Syndrome Fibroblasts Protein Serine-Threonine Kinases Radiation Tolerance Cell Line Ataxia Telangiectasia Checkpoint Kinase 2 Chromosomes Human Humans Abnormalities Multiple Phosphorylation Tumor Suppressor Protein p53 Interphase Protein Kinases DNA Damage |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0008-5472 |
| Popis: | Cells derived from Nijmegen Breakage Syndrome (NBS) patients display radiosensitivity and cell cycle checkpoint defects. Here, we examine whether the radiosensitivity of NBS cells is the result of a repair defect or whether it can be attributed to impaired checkpoint arrest. We report a small increased fraction of unrejoined double strand breaks and, more significantly, increased chromosome breaks in noncycling NBS cells at 24 h after irradiation. One of the NBS lines examined (347BR) was atypical in showing a nearly normal checkpoint response. In contrast to the mild checkpoint defect, 347BR displays marked y-ray sensitivity similar to that shown by other NBS lines. Thus, the gamma-ray sensitivity correlates with the repair defect rather than impaired checkpoint control. Taken together, the results provide direct evidence for a repair defect in NBS cells and are inconsistent with the suggestion that the radiosensitivity is attributable only to impaired checkpoint arrest. 347BR also displays elevated spontaneous damage that cannot be attributed to impaired G2-M arrest, suggesting a function of Nbsl in decreasing or limiting the impact of spontaneously arising double strand breaks. |
| Databáze: | OpenAIRE |
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