A DNA double-strand break defective fibroblast cell line (180BR) derived from a radiosensitive patient represents a new mutant phenotype
| Autor: | Badie C, Goodhardt M, Waugh A, Doyen N, Foray N, Patrick Calsou, Singleton B, Gell D, Salles B, Jeggo P, Cf, Arlett, Ep, Malaise |
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| Předmět: |
Cell Nucleus
Recombination Genetic Cell Survival Cell Cycle Genetic Complementation Test Nuclear Proteins Dose-Response Relationship Radiation DNA-Activated Protein Kinase Fibroblasts Precursor Cell Lymphoblastic Leukemia-Lymphoma Protein Serine-Threonine Kinases Radiation Tolerance DNA-Binding Proteins Kinetics Phenotype Gamma Rays DNA Nucleotidyltransferases Tumor Cells Cultured Humans Cobalt Radioisotopes VDJ Recombinases Cell Line Transformed DNA Damage |
| Zdroj: | Scopus-Elsevier Europe PubMed Central |
| Popis: | The 180BR cell line was derived from an acute lymphoblastic leukemia patient who overresponded to radiation therapy and died following radiation morbidity. 180BR cells are hypersensitive to the lethal effects of ionizing radiation and are defective in the repair of DNA double-strand breaks (DSBs). The levels and activity of the proteins of the DNA-dependent protein kinase complex are normal in 180BR cells. To facilitate a measurement of V(D)J recombination, we have characterized 180BRM, a SV40-transformed line derived from 180BR. 180BRM retains the radiosensitivity and defect in DSB repair characteristic of 180BR. The activities associated with DNA-dependent protein kinase are also normal in 180BRM cells. The ability to carry out V(D)J recombination is comparable in 180BRM and a reference control transformed human cell line, MRC5V1. These results show that 180BR and 180BRM differ from the rodent mutants belonging to ionizing radiation complementation groups 4, 5, 6, and 7 and, therefore, represent a new mutant phenotype, in which a defect in DNA DSB rejoining is not associated with defective V(D)J recombination. Furthermore, we have shown that 180BR can arrest at the G1-S and G2-M cell cycle checkpoints after irradiation. These results confirm that 180BR can be distinguished from ataxia telangiectasia. |
| Databáze: | OpenAIRE |
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