Publication Type:

Journal Article


Science Signaling, Volume 4, Number 167 (2011)



antioxidant, article, ataxia telangiectasia, ATM protein, cell cycle, cell cycle protein, Cell Cycle Proteins, chemical structure, chemistry, dimerization, DNA binding protein, DNA damage, DNA dependent protein kinase, DNA strand breakage, DNA-Activated Protein Kinase, DNA-Binding Proteins, DsbA protein, gene mutation, human, Humans, ionizing radiation, Mammalia, mammalian target of rapamycin, metabolism, Models, Molecular, nerve cell, Neurons, neuropathology, nonhuman, oxidation, oxidation reduction reaction, Oxidation-Reduction, oxidative stress, pathology, physiology, priority journal, protein serine threonine kinase, Protein-Serine-Threonine Kinases, reactive oxygen metabolite, Reactive Oxygen Species, redox effector factor 1, review, signal transduction, target of rapamycin kinase, TOR Serine-Threonine Kinases, tumor suppressor protein, Tumor Suppressor Proteins


Ataxia-telangiectasia (A-T) is a rare, neurodegenerative, inherited disease arising from mutations in the kinase A-T mutated (ATM), which promotes cell cycle checkpoints and DNA double-strand break repair. Puzzlingly, these ATM activities fail to fully explain A-T neuropathologies, which instead have links to stress induced by reactive oxygen species (ROS). However, a landmark discovery reveals an unexpected intersection of ROS and kinase signaling: ATM can be directly activated by oxidation to form a disulfide-linked dimer in a mechanism distinct from DNA damage activation. When combined with notable structural-based insights into the ATM homolog DNA-PK (DNA-protein kinase) and mTOR (mammalian target of rapamycin), these results suggest conformation and assembly mechanisms to signal oxidative stress through an ATM nodal point. These findings fundamentally affect our understanding of ROS and ATM signaling and of the A-T phenotype, with implications for altering signaling in cancer cells to increase sensitivities to current therapeutic interventions. © 2011 American Association for the Advancement of Science. All Rights Reserved.


cited By (since 1996)9

Cite this Research Publication

J. J. Pab Perry and Tainer, J. Aac, “All stressed out without ATM kinase”, Science Signaling, vol. 4, 2011.