ATM deficiency and oxidative stress: A new dimension of defective response to DNA damage

Ari Barzilai, Galit Rotman, Yosef Shiloh*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

321 Scopus citations


ATM is one of the sentries at the gate of genome stability. This multifunctional protein kinase orchestrates the intricate array of cellular responses to DNA double-strand breaks. Absence or inactivation of ATM leads to the pleiotropic genetic disorder ataxia-telangiectasia (A-T), whose hallmarks are neuronal degeneration, immunodeficiency, genomic instability, premature aging and cancer predisposition. Several features of the complex clinical and cellular phenotype of A-T are reminiscent of other syndromes involving neurodegeneration, premature aging or genomic instability. A common denominator of many of these conditions is the perturbation of the cellular balance of reactive oxygen species, which leads to constant oxidative stress. Of these disorders, ATM deficiency is one of the most extensively studied with regard to the genome instability-oxidative stress connection. This connection may provide new insights into the phenotypes associated with genetic deficiencies of DNA damage responses, and point to new strategies to alleviate some of their clinical symptoms.

Original languageEnglish
Pages (from-to)3-25
Number of pages23
JournalDNA Repair
Issue number1
StatePublished - 2002


FundersFunder number
National Institutes of Health
National Institute of Neurological Disorders and StrokeR01NS031763
Israel Science Foundation


    • ATM
    • Ataxia-telangiectasia
    • DNA double strand breaks
    • Oxidative stress
    • Reactive oxygen species


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