X-ray-induced genomic instability in Atm knock-out mouse cells

抄録

The gene responsible for ataxia telangiectasia (AT) encodes ATM protein that plays a major role in the network of a signal transduction initiated by DNA-double strand breaks. To elucidate how radiation-induced genomic instability is modulated by dysfunction of ATM protein, we examined delayed chromosomal instability in individual cell lines established from wild type Atm^+/+ , heterozygote Atm^+/- and knock out Atm^−/- mouse embryos. The Atm^−/- mouse cells show elevated chromosomal and telomeric instability compared with Atm^+/+ mouse cells. The telomeric instability was characterized by the abnormal telomere FISH signals including loss and gain of the signals in the end of chromosome. This suggests that Atm deficiency makes telomeres vulnerable to breakage. Thus, the present study shows that ATM protein plays an essential role to maintain telomere integrity and prevent chromosomes from end-to-end fusions. [J Radiat Res 44:441 (2003)]