title: X-ray-induced telomeric instability in Atm-deficient mouse cells.
abstract: The gene responsible for ataxia telangiectasia (AT) encodes ATM protein, which plays a major role in the network of a signal transduction initiated by double strand DNA breaks. To determine how radiation-induced genomic instability is modulated by the dysfunction of ATM protein, we examined radiation-induced delayed chromosomal instability in individual cell lines established from wild-type Atm(+/+), heterozygote Atm(+/-), and knock-out Atm(-/-) mouse embryos. The results indicate that Atm(-/-) mouse cells are highly susceptible to the delayed induction of telomeric instability and end-to-end chromosome fusions by radiation in addition to the elevated spontaneous telomeric instability detected by telomere fluorescence in situ hybridization (FISH). The telomeric instability was characterized by abnormal telomere FISH signals, including loss of the signals and the extra-chromosomal signals that were associated and/or not associated with chromosome ends, suggesting that Atm deficiency makes telomeres vulnerable to breakage. Thus, the present study shows that Atm protein plays an essential role in maintaining telomere integrity and prevents chromosomes from end-to-end fusions, indicating that telomeres are a target for the induction of genomic instability by radiation.
authors.affiliation: Laboratory of Radiation Biology, Department of Radiology and Radiation Biology, Course of Life Sciences and Radiation Research, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
authors.forename: Barkhaa
authors.initials: B
authors.lastname: Undarmaa
authors.forename: Seiji
authors.initials: S
authors.lastname: Kodama
authors.forename: Keiji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Otsura
authors.initials: O
authors.lastname: Niwa
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D016923:Cell Death / Q000528:radiation effects; D002460:Cell Line; D002869:Chromosome Aberrations / Q000528:radiation effects; D003584:Cytological Techniques / Q000379:methods; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D004622:Embryo, Mammalian / Q000166:cytology; D042822:Genomic Instability / Q000502:physiology; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics; D011836:Radiation Tolerance; D016615:Telomere / Q000737:chemistry / Q000235:genetics* / Q000528:radiation effects*; D025521:Tumor Suppressor Proteins; D014965:X-Rays / Q000009:adverse effects*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases