1. Involvement of telomere dysfunction in the induction of genomic instability by radiation in scid mouse cells.
- Author
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Urushibara A, Kodama S, Suzuki K, Desa MB, Suzuki F, Tsutsui T, and Watanabe M
- Subjects
- Animals, Cell Line, Chromosomal Instability radiation effects, Chromosome Aberrations, DNA Damage, DNA-Activated Protein Kinase, Dose-Response Relationship, Radiation, In Situ Hybridization, Fluorescence, Mice, Mice, SCID, Protein Serine-Threonine Kinases metabolism, Radiation Tolerance genetics, Telomere genetics, Telomere pathology, DNA-Binding Proteins, Genomic Instability radiation effects, Telomere radiation effects
- Abstract
To determine the effects of a defect in NHEJ on the induction of genomic instability by radiation, we investigated X-ray-induced delayed chromosomal aberrations such as dicentrics and fragments in scid mouse cells. We found that radiosensitive scid mouse cells are more susceptible than wild-type mouse cells to the induction of delayed chromosomal aberrations when the cells are exposed to an equivalent survival dose of X-rays. Telomere FISH analysis revealed that radiation enhances the induction of telomeric fusions where telomeric sequences remain at the fused position (tel+ end-fusions), suggesting that radiation induces telomere dysfunction. Moreover, formation of the tel+ end-fusions was found to be enhanced in scid mouse cells, suggesting that DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a role in telomeric stabilization. Thus, the present study suggests that a cause of genomic instability is telomere dysfunction induced by radiation and that a defect in DNA-PKcs enhances the telomeric destabilization.
- Published
- 2004
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