Cellular localisation of the ataxia-telangiectasia (ATM) gene product and discrimination between mutated and normal forms

D Watters; K K Khanna; H Beamish; G Birrell; K Spring; P Kedar; M Gatei; D Stenzel; K Hobson; S Kozlov; N Zhang; A Farrell; J Ramsay; R Gatti; M Lavin

doi:10.1038/sj.onc.1201037

Cellular localisation of the ataxia-telangiectasia (ATM) gene product and discrimination between mutated and normal forms

Oncogene. 1997 Apr 24;14(16):1911-21. doi: 10.1038/sj.onc.1201037.

Authors

D Watters¹, K K Khanna, H Beamish, G Birrell, K Spring, P Kedar, M Gatei, D Stenzel, K Hobson, S Kozlov, N Zhang, A Farrell, J Ramsay, R Gatti, M Lavin

Affiliation

¹ Queensland Institute of Medical Research, P.O. Royal Brisbane Hospital, Herston, Australia.

PMID: 9150358
DOI: 10.1038/sj.onc.1201037

Abstract

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 approximately 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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Antibodies
Ataxia Telangiectasia / genetics*
Ataxia Telangiectasia Mutated Proteins
Blotting, Western
Cell Cycle Proteins
Cell Line, Transformed
Cell Nucleus / ultrastructure
Cloning, Molecular
Cytoplasmic Granules / ultrastructure
DNA-Binding Proteins
Enzyme-Linked Immunosorbent Assay
Herpesvirus 4, Human
Homozygote
Humans
Microscopy, Immunoelectron
Microsomes / ultrastructure
Open Reading Frames
Organelles / metabolism
Organelles / ultrastructure*
Point Mutation*
Protein Biosynthesis*
Protein Serine-Threonine Kinases*
Proteins / analysis
Recombinant Proteins / analysis
Recombinant Proteins / biosynthesis
Sequence Deletion
Tumor Suppressor Protein p53 / analysis
Tumor Suppressor Proteins

Substances

Antibodies
Cell Cycle Proteins
DNA-Binding Proteins
Proteins
Recombinant Proteins
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
ATM protein, human
Ataxia Telangiectasia Mutated Proteins
Protein Serine-Threonine Kinases