title: Involvement of telomere dysfunction in the induction of genomic instability by radiation in scid mouse cells.
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.
authors.affiliation: Division of Radiation Biology, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Urushibara
authors.forename: Seiji
authors.initials: S
authors.lastname: Kodama
authors.forename: Keiji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Mohamad Bin Md
authors.initials: MB
authors.lastname: Desa
authors.forename: Fumio
authors.initials: F
authors.lastname: Suzuki
authors.forename: Takeki
authors.initials: T
authors.lastname: Tsutsui
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002460:Cell Line; D043171:Chromosomal Instability / Q000528:radiation effects; D002869:Chromosome Aberrations; D004249:DNA Damage; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D042822:Genomic Instability / Q000528:radiation effects*; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D016513:Mice, SCID; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics; D016615:Telomere / Q000235:genetics / Q000473:pathology / Q000528:radiation effects*
chemical_list: D004268:DNA-Binding Proteins; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases