¹The Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, P.O. Royal Brisbane Hospital, Herston, Brisbane 4029, Australia

²Analytical Electron Microscope Facility, Queensland University of Technology, Gardens Point, George Street, Brisbane, 4000, Australia

³Queensland Radium Institute, Royal Brisbane Hospital, Herston Road, Brisbane 4029, Australia

⁴Department of Pathology, Centre for Health Sciences, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, USA

⁵Department of Surgery, University of Queensland, Royal Brisbane Hospital, Herston, Brisbane 4029, Australia

^aAuthor for correspondence

The recently cloned gene (ATM) mutated in the human genetic disorder ataxia-telangiectasia (A-T) is involved in DNA damage response at different 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 immunofluorescence 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.

ataxia-telangiectasia; cellular localisation; mutations; radiation; p53