Localization of a portion of extranuclear ATM to peroxisomes.

The gene mutated in the human genetic disorder ataxia-telangiectasia codes for a protein, ATM, the known functions of which include response to DNA damage, cell cycle control, and meiotic recombination. Consistent with these functions, ATM is predominantly present in the nucleus of proliferating cells; however, a significant proportion of the ...
protein has also been detected outside the nucleus in cytoplasmic vesicles. To understand the possible role of extra-nuclear ATM, we initially investigated the nature of these vesicles. In this report we demonstrate that a portion of ATM co-localizes with catalase, that ATM is present in purified mouse peroxisomes, and that there are reduced levels of ATM in the post-mitochondrial membrane fraction of cells from a patient with a peroxisome biogenesis disorder. Furthermore the use of the yeast two-hybrid system demonstrated that ATM interacts directly with a protein involved in the import of proteins into the peroxisome matrix. Because peroxisomes are major sites of oxidative metabolism, we investigated catalase activity and lipid hydroperoxide levels in normal and A-T fibroblasts. Significantly decreased catalase activity and increased lipid peroxidation was observed in several A-T cell lines. The localization of ATM to peroxisomes may contribute to the pleiotropic nature of A-T.
Mesh Terms:
Amino Acid Sequence, Animals, Ataxia Telangiectasia, Catalase, Cell Cycle Proteins, Cell Line, Cell Nucleus, DNA-Binding Proteins, Fibroblasts, Humans, Immunohistochemistry, Lipid Peroxides, Male, Mice, Molecular Sequence Data, Peroxisomal Disorders, Peroxisomes, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins, Sequence Alignment, Tumor Suppressor Proteins, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Nov. 26, 1999
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