Abstract
A gene mutated in the human genetic disorder ataxia-telangiectasia (A-T), ATM, was recently identified by positional cloning. ATM is a member of the phosphatidylinositol-3-kinase superfamily, some of which are protein kinases and appear to have important roles in cell cycle control and radiation signal transduction. We describe herein, to our knowledge, for the first time, the cloning of a full-length cDNA for ATM and correction of multiple aspects of the radio-sensitive phenotype of A-T cells by transfection with this cDNA. Overexpression of ATM cDNA in A-T cells enhanced the survival of these cells in response to radiation exposure, decreased radiation-induced chromosome aberrations, reduced radio-resistant DNA synthesis, and partially corrected defective cell cycle checkpoints and induction of stress-activated protein kinase. This correction of the defects in A-T cells provides further evidence of the multiplicity of effector functions of the ATM protein and suggests possible approaches to gene therapy.
Bibliography
Zhang, N., Chen, P., Khanna, K. K., Scott, S., Gatei, M., Kozlov, S., Watters, D., Spring, K., Yen, T., & Lavin, M. F. (1997). Isolation of full-length ATM cDNA and correction of the ataxia-telangiectasiaâcellularâphenotype. Proceedings of the National Academy of Sciences, 94(15), 8021â8026.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:31 a.m.) |
Deposited | 3 years, 4 months ago (April 13, 2022, 3:09 p.m.) |
Indexed | 1 year, 1 month ago (July 21, 2024, 3:11 a.m.) |
Issued | 28 years, 1 month ago (July 22, 1997) |
Published | 28 years, 1 month ago (July 22, 1997) |
Published Online | 28 years, 1 month ago (July 22, 1997) |
Published Print | 28 years, 1 month ago (July 22, 1997) |
@article{Zhang_1997, title={Isolation of full-length ATM cDNA and correction of the ataxia-telangiectasia cellular phenotype}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.15.8021}, DOI={10.1073/pnas.94.15.8021}, number={15}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Zhang, Ning and Chen, Philip and Khanna, Kum Kum and Scott, Shaun and Gatei, Magtouf and Kozlov, Sergei and Watters, Dianne and Spring, Kevin and Yen, Tim and Lavin, Martin F.}, year={1997}, month=jul, pages={8021–8026} }