Involvement of telomere dysfunction in the induction of genomic instability by radiation in scid mouse cells.
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.
Urushibara
Ayumi
A
Division of Radiation Biology, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Kodama
Seiji
S
Suzuki
Keiji
K
Desa
Mohamad Bin Md
MB
Suzuki
Fumio
F
Tsutsui
Takeki
T
Watanabe
Masami
M
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*
D004268:DNA-Binding Proteins; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases