The recently cloned gene (ATM) mutated in the human genetic disorder ataxia-telangiectasia (A-T) is involved in DNA damage response at dierent cell cycle checkpoints and also appears to have a wider role in signal transduction. Antibodies prepared against peptides from the predicted protein sequence detected a * 350 kDa protein corresponding to the open reading frame, which was absent in 13/23 A-T homozygotes. Subcellular fractionation, immunoelectronmicroscopy and immunouorescence showed that the ATM protein is present in the nucleus and cytoplasmic vesicles. This distribution did not change after irradiation. We also provide evidence that ATM protein binds to p53 and this association is defective in A-T cells compatible with the defective p53 response in these cells. These results provide further support for a role for the ATM protein as a sensor of DNA damage and in a more general role in cell signalling, compatible with the broader phenotype of the syndrome.
Wide-field fluorescence microscopy at high magnification was used to study the intracellular binding site of Rubb 16 in Escherichia coli. Upon incubation of E. coli cells at the minimum inhibitory concentration, Rubb 16 localised at ribosomes with no significant DNA binding observed. Furthermore, Rubb 16 condensed the ribosomes when they existed as polysomes. It is postulated that the condensation of polysomes would halt protein production, and thereby inhibit bacterial growth. The results of this study indicate that the family of inert dinuclear ruthenium complexes Rubb n selectively target RNA over DNA in vivo. Selective RNA targeting could be advantageous for the development of therapeutic agents, and because of differences in ribosome structure between bacteria and eukaryotic cells, the Rubb n complexes could be selectively toxic to bacteria. In support of this hypothesis, the toxicity of Rubb 16 was found to be significantly less to liver and kidney cell lines than against a range of bacteria.
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