Role of DNA-PK in the process of aberration formation as studied in irradiated human glioblastoma cell lines M059K and M059J
| Autor: | Margret Rave-Fränk, Patricia Virsik-Köpp, Hana Hofman-Hüther, Heinz Schmidberger |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
DNA damage
Chromosomal translocation DNA-Activated Protein Kinase Protein Serine-Threonine Kinases Biology Wortmannin 03 medical and health sciences Dicentric chromosome chemistry.chemical_compound 0302 clinical medicine Tumor Cells Cultured Humans Radiology Nuclear Medicine and imaging 030304 developmental biology Chromosome Aberrations Genetics 0303 health sciences Radiological and Ultrasound Technology Kinase Nuclear Proteins Chromosome Molecular biology Androstadienes DNA-Binding Proteins chemistry Cell culture 030220 oncology & carcinogenesis Glioblastoma DNA DNA Damage |
| Zdroj: | International Journal of Radiation Biology. 79:61-68 |
| ISSN: | 1362-3095 0955-3002 |
| DOI: | 10.1080/0955300021000038644 |
| Popis: | The participation of various DNA double-strand break repair mechanisms in the formation of chromosome aberrations is not yet fully understood. To investigate particularly the role of non-homologous end-joining, we analysed the formation of radiation-induced aberrations in a DNA-protein kinase (PK(CS))-proficient cell line M059K and in a deficient cell line M059J.Plateau-phase M059K and M059J cells were irradiated with low doses of X-rays. Chromosome aberrations were determined as genomic yields of dicentric chromosomes and excess acentric fragments, scored in Giemsa-stained metaphases, and as partial yields of reciprocal translocations and total visible complex exchanges (complex aberrations) for chromosomes 4, 7 and 11 using the FISH method. M059K cells were also analysed in the presence of 50 micro m wortmannin, a DNA-PK inhibitor.DNA-PK-deficient cells showed a higher yield of simple stable and unstable and of complex aberrations in comparison with DNA-PK-proficient cells. The largest differences were observed for excess acentric fragments and for complex aberrations. DNA-PK inhibition by wortmannin in M059-K cells resulted in increased aberration yield in the same qualitative and quantitative manner as in M059-J cells.The results obtained with DNA-PK-deficient M059J cells and with DNA-PK-proficient M059K cells treated with wortmannin, an inhibitor of DNA-PK and ATM, suggest that the elimination of DNA-PK-dependent non-homologous end-joining can recruit a slow, error-prone repair process, which is DNA-PK independent and favours the increased formation of chromosome aberrations. The nature of this pathway and the way of its participation in aberration formation need further elucidation. |
| Databáze: | OpenAIRE |
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