The many substrates and functions of ATM

@article{Kastan2000TheMS,
  title={The many substrates and functions of ATM},
  author={Michael B. Kastan and Dae-Sik Lim},
  journal={Nature Reviews Molecular Cell Biology},
  year={2000},
  volume={1},
  pages={179-186}
}
  • M. Kastan, D. Lim
  • Published 1 December 2000
  • Biology
  • Nature Reviews Molecular Cell Biology
As its name suggests, the ATM ? 'ataxia-telangiectasia, mutated' ? gene is responsible for the rare disorder ataxia-telangiectasia. Patients show various abnormalities, mainly in their responses to DNA damage, but also in other cellular processes. Although it is hard to understand how a single gene product is involved in so many physiological processes, a clear picture is starting to emerge. 
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The recent findings on the molecular mechanisms of ATM in DDR, the mitotic spindle checkpoint, as well as hyperactive ATM signaling in cancer invasion and metastasis are discussed.
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Two methods that have been developed in the lab to assess the radiosensitivity of A-T patients are described: Colony Survival Assay (CSA) and Flow Cytometry of phospho-SMC1 (FC-pSMC 1).
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Understanding the biology of AT will lead to a greater understanding of the fundamental processes that underpin cancer and neurodegeneration, as well as inspire new ideas on how to prevent cancer.
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It has now been demonstrated that mutations in ATM lead to defective telomere maintenance in mammalian cells, and how ATM and telomeres serve as controllers of cellular responses to DNA damage is reviewed.
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It is proposed that the ATM-dependent control of TNKS1 function, independently of DDR, could explain several A-T features and shed light on new therapeutic approaches for the A- T syndrome.
Dual role of Nbs1 in the ataxia telangiectasia mutated‐dependent DNA damage response
TLDR
Nbs1 acts both as a downstream target of ataxia telangiectasia mutated in the S‐phase checkpoint of the cell cycle as well as an upstream modulator or activator of atAXiaTelangiECTasia mutatedInsight into the functions of Nbs1 in the DNA damage response mediated by the protein kinase is provided.
ATM and ataxia telangiectasia Second in Molecular Medicine Review Series
TLDR
Biological analysis of this protein kinase has shown that it is a crucial nexus for the cellular response to DNA double-stranded breaks and will lead to a greater understanding of the fundamental processes that underpin cancer and neurodegeneration.
An HTRF® Assay for the Protein Kinase ATM.
TLDR
Using a purified, functionally active recombinant ATM and one of its physiological substrates, p53, an in vitro FRET-based activity assay that is suitable for high-throughput drug screening is developed.
Ataxia telangiectasia: new neurons and ATM.
Cellular functions of the protein kinase ATM and their relevance to human disease.
TLDR
Recent structural insights into ATM regulation, and possible aetiologies of A-T phenotypes, are discussed, including reactive oxygen species, mitochondrial dysfunction, alterations in transcription, R-loop metabolism and alternative splicing, defects in cellular proteostasis and metabolism, and potential pathogenic roles for hyper-poly(ADP-ribosyl)ation.
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TLDR
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TLDR
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TLDR
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