| Author(s) | Hande MP; Balajee AS; Tchirkov A; Wynshaw-Boris A; Lansdorp PM
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| Title | Extra-chromosomal telomeric DNA in cells from Atm(-/-) mice and patients with ataxia-telangiectasia
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| Source | HUMAN MOLECULAR GENETICS 10 (5): 519-528
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| Date | 2001 MAR 1
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| Type | Journal : Article
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| LCR: 23 NCR: 40 LCS: 26 GCS: 47
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| Address | British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada.
Columbia Univ Coll Phys & Surg, Ctr Radiol Res, New York, NY 10032 USA.
Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA.
Univ British Columbia, Dept Med, Vancouver, BC V6T 2B5, Canada.
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| Reprint | Lansdorp, PM, British Columbia Canc Agcy, Terry Fox Lab, 601 W 10th
Ave, Vancouver, BC V5Z 1L3, Canada.
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| Abstract | Ataxia-telangiectasia (AT) is an autosomally recessive human genetic disease with pleiotropic defects such as neurological degeneration, immunodeficiency, chromosomal instability, cancer susceptibility and premature aging. Cells derived from AT patients and ataxia-telangiectasia mutated (ATM)-deficient mice show slow growth in culture and premature senescence. ATM, which belongs to the P13 kinase family along with DNA-PK, plays a major role in signaling the p53 response to DNA strand breaks. Telomere maintenance is perturbed in yeast strains lacking genes homologous to ATM and cells from patients with AT have short telomeres. We examined the length of individual telomeres in cells from Atm(-/-) mice by fluorescence in situ hybridization. Telomeres were extensively shortened in multiple tissues of Atm(-/-) mice. More than the expected number of telomere signals was observed in interphase nuclei of Atm(-/-) mouse fibroblasts. Signals corresponding to 5-25 kb of telomeric DNA that were not associated with chromosomes were also noticed in Atm(-/-) metaphase spreads. Extrachromosomal telomeric DNA was also detected in fibroblasts from AT patients and may represent fragmented telomeres or by-products of defective replication of telomeric DNA. These results suggest a role of ATM in telomere maintenance and replication, which may contribute to the poor growth of Atm(-/-) cells and increased tumor incidence in both AT patients and Atm(-/-) mice.
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