The many substrates and functions of ATM

  title={The many substrates and functions of ATM},
  author={Michael B. Kastan and Dae-Sik Lim},
  journal={Nature Reviews Molecular Cell Biology},
  • 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. 
The versatile functions of ATM kinase
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.
ATM Kinase
  • S. Kozlov
  • Biology, Medicine
    Methods in Molecular Biology
  • 2017
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).
ATM and ataxia telangiectasia
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.
ATM function and telomere stability
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.
“A DNA Damage Response (DDR) –independent Role for the Ataxia-Telangiectasia Mutated (ATM) Gene Product"
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
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
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.
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.
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.


Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart.
  • Y. Shiloh
  • Biology
    Annual review of genetics
  • 1997
The recent identification of the gene responsible for Ataxia-telangiectasia, ATM, has revealed its product to be a large, constitutively expressed phosphoprotein with a carboxy-terminal region similar to the catalytic domain of phosphatidylinositol 3-Kinases (PI 3-kinases).
A single ataxia telangiectasia gene with a product similar to PI-3 kinase.
A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia was identified by positional cloning on chromosome 11q22-23 and encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control.
The genetic defect in ataxia-telangiectasia.
The pleiotropic nature of the clinical and cellular phenotype suggests that the gene product involved is important in maintaining stability of the genome but also plays a more general role in signal transduction.
ATM binds to β-adaptin in cytoplasmic vesicles
The data describing the association of ATM with β-adaptin in vesicles indicate that ATM may play a role in intracellular vesicle and/or protein transport mechanisms.
Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products
A biochemical link between cell-cycle checkpoints activated by DNA damage and DNA repair in two genetic diseases with overlapping phenotypes is demonstrated.
ATM-dependent phosphorylation of nibrin in response to radiation exposure
It is demonstrated that nibrin is phosphorylated within one hour of treatment of cells with IR, and ATM physically interacts with and phosphorylatesnibrin on serine 343 both in vivo and in vitro.
Enhanced phosphorylation of p53 by ATM in response to DNA damage.
Various damage-induced responses may be activated by enhancement of the protein kinase activity of ATM, and this activity was markedly enhanced within minutes after treatment of cells with a radiomimetic drug.
Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation.
It is shown that the ATM protein kinase directly phosphorylates T68 within the SQ/TQ-rich domain of Chk2 in vitro and that T68 is phosphorylated in vivo in response to IR in an ATM-dependent manner.