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ATM, telomeres and aging

Double knockout mice demonstrate link between ATM and telomere state in disease pathology.

Jonathan Weitzman(jonathanweitzman@hotmail.com)

ATM — the product of the gene mutated in ataxia-telangiectasia (A-T) — is involved in the cellular response to DNA damage and has been implicated in telomere maintenance. Atm mutant mice display modest aging and growth retardation defects compared to A-T patients. In an Advanced Online Publication in Nature, Kwok-Kin Wong and colleagues describe studies in mice to assess the interaction between ATM and telomeres (Nature, DOI:10.1038/nature01385, 22 January, 2003).

Wong et al. bred Atm-deficient mice with animals lacking the telomerase RNA component (Terc). Double knockout mice showed an increase in genomic instability and chromosomal fusions, and premature lethality. Cell proliferation defects were also observed in primary cells in culture and in several stem cell populations in vivo. The interaction between telomeres and ATM, and the impaired stem-cell reserve, explains the multi-organ affects in A-T patients.

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