ATM, a paradigm for a stress-responsive signal transducer in higher vertebrate cells.
ATM, the gene mutated in ataxia telangiectasia, is related to a family of large phosphatidylinositol 3-kinase domain-containing protein kinases involved in cell cycle control and DNA repair. To define the physiological roles of ATM in higher vertebrate cells, we created an ATM-deficient DT40 cell line, which, despite of the lack of p53 expression, displays multiple p53-independent defects in cell cycle checkpoint control and in maintenance of chromosomal DNA. ATM -/- DT40 cells also show a mild impairment in homologous recombination repair, which is independent of its checkpoint control defects. These ATM deficient DT40 clones thus provide a useful model system for analyzing p53-independent ATM functions in cellular response to double-strand break. Furthermore, we observe various abnormalities in cellular response to noxious stress such as oxidative stress in ATM -/- DT40 cells, indicating that ATM plays important roles not only in cellular response to DNA damage but also in the maintenance of the cell homeostasis in response to oxidative damage.
Yamamoto
Ken-ichi
K
Department of Molecular Pathology, Center for the Development of Molecular Target Drugs, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-0934, Japan.
Kobayashi
Masahiko
M
Shimizu
Hiroko
H
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D001402:B-Lymphocytes / Q000166:cytology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases