ATM Activation by Oxidative Stress

@article{Guo2010ATMAB,
  title={ATM Activation by Oxidative Stress},
  author={Zhi Guo and Sergei V. Kozlov and Martin F. Lavin and Maria D. Person and Tanya T. Paull},
  journal={Science},
  year={2010},
  volume={330},
  pages={517 - 521}
}
Stress, DNA Damage, and ATM The protein kinase ATM (ataxia-telangiectasia mutated) is a key component of the signaling pathway through which cells are protected from DNA damage. ATM becomes activated within a protein complex at sites of double-stranded breaks in DNA. ATM is also activated in response to increased production of reactive oxygen species (ROS). Such activation was thought to reflect DNA damage caused by ROS, but Guo et al. (p. 517) showed that ATM was in fact directly activated by… Expand

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Interventional Clinical Trial
Study design: Parallel group, placebo-controlled, dose-escalation each 2 months for 12 months. Dose based on percent (%) of calculated caloric intake. Thirty participants will be… Expand
ConditionsAtaxia Telangiectasia
InterventionDietary Supplement
ATM activation in the presence of oxidative stress
TLDR
It is shown that ATM activation by DSBs is inhibited in the presence of H2O2 because oxidation blocks the ability of MRN to bind to DNA, however, ATM activation via direct oxidation by H2 O2 complements the loss of MRn/DSB-dependent activation and contributes significantly to the overall level of ATM activity. Expand
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TLDR
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TLDR
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References

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TLDR
PP5 plays an essential role in the activation and checkpoint signaling functions of ATM in cells that have suffered DNA double-strand breaks, and a direct regulatory linkage between PP5 and ATM is reported. Expand
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TLDR
Some of the cellular responses to alterations in the cellular redox state during hypoxia or oxidative stress are described, which appears to be the simplest of the three excision repair pathways. Expand
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TLDR
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TLDR
It is shown that functional MRN is required for ATM activation, and consequently for timely activation of ATM‐mediated pathways, and explain the clinical resemblance between A‐T and A-TLD. Expand
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
It is concluded that there are at least three functionally important radiation‐induced autophosphorylation events in ATM, including autoph phosphorylation on pS367 and pS1893, which are physiologically important parts of the DNA damage response. Expand
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