DOI: 10.1073/pnas.96.20.11134. Purification and DNA binding properties of the ataxia-telangiectasia gene product ATM

Purification and DNA binding properties of the ataxia-telangiectasia gene product ATM

10.1073/pnas.96.20.11134

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The human neurodegenerative and cancer predisposition condition ataxia-telangiectasia is characterized at the cellular level by radiosensitivity, chromosomal instability, and impaired induction of ionizing radiation-induced cell cycle checkpoint controls. Recent work has revealed that the gene defective in ataxia-telangiectasia, termed ATM , encodes an ≈350-kDa polypeptide, ATM, that is a member of the phosphatidylinositol 3-kinase family. We show that ATM binds DNA and exploit this to purify ATM to near homogeneity. Atomic force microscopy reveals that ATM exists in two populations, with sizes consistent with monomeric and tetrameric states. Atomic force microscopy analyses also show that ATM binds preferentially to DNA ends. This property is similar to that displayed by the DNA-dependent protein kinase catalytic subunit, a phosphatidylinositol 3-kinase family member that functions in DNA damage detection in conjunction with the DNA end-binding protein Ku. Furthermore, purified ATM contains a kinase activity that phosphorylates serine-15 of p53 in a DNA-stimulated manner. These results provide a biochemical assay system for ATM, support genetic data indicating distinct roles for DNA-dependent protein kinase and ATM, and suggest how ATM may signal the presence of DNA damage to p53 and other downstream effectors.

Bibliography

Smith, G. C. M., Cary, R. B., Lakin, N. D., Hann, B. C., Teo, S.-H., Chen, D. J., & Jackson, S. P. (1999). Purification and DNA binding properties of the ataxia-telangiectasia gene product ATM. Proceedings of the National Academy of Sciences, 96(20), 11134â11139.

Authors 7

Graeme C. M. Smith (first)
Robert B. Cary (additional)
Nicholas D. Lakin (additional)
Byron C. Hann (additional)
Soo-Hwang Teo (additional)
David J. Chen (additional)
Stephen P. Jackson (additional)

References 38 Referenced 133

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:41 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:51 p.m.)
Indexed	1 year, 2 months ago (June 24, 2024, 2:33 p.m.)
Issued	25 years, 11 months ago (Sept. 28, 1999)
Published	25 years, 11 months ago (Sept. 28, 1999)
Published Online	25 years, 11 months ago (Sept. 28, 1999)
Published Print	25 years, 11 months ago (Sept. 28, 1999)

Funders 0

None

BibTeX

@article{Smith_1999, title={Purification and DNA binding properties of the ataxia-telangiectasia gene product ATM}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.20.11134}, DOI={10.1073/pnas.96.20.11134}, number={20}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Smith, Graeme C. M. and Cary, Robert B. and Lakin, Nicholas D. and Hann, Byron C. and Teo, Soo-Hwang and Chen, David J. and Jackson, Stephen P.}, year={1999}, month=sep, pages={11134–11139} }

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  "abstract": "<jats:p>\n            The human neurodegenerative and cancer predisposition condition ataxia-telangiectasia is characterized at the cellular level by radiosensitivity, chromosomal instability, and impaired induction of ionizing radiation-induced cell cycle checkpoint controls. Recent work has revealed that the gene defective in ataxia-telangiectasia, termed\n            <jats:italic>ATM</jats:italic>\n            , encodes an \u2248350-kDa polypeptide, ATM, that is a member of the phosphatidylinositol 3-kinase family. We show that ATM binds DNA and exploit this to purify ATM to near homogeneity. Atomic force microscopy reveals that ATM exists in two populations, with sizes consistent with monomeric and tetrameric states. Atomic force microscopy analyses also show that ATM binds preferentially to DNA ends. This property is similar to that displayed by the DNA-dependent protein kinase catalytic subunit, a phosphatidylinositol 3-kinase family member that functions in DNA damage detection in conjunction with the DNA end-binding protein Ku. Furthermore, purified ATM contains a kinase activity that phosphorylates serine-15 of p53 in a DNA-stimulated manner. These results provide a biochemical assay system for ATM, support genetic data indicating distinct roles for DNA-dependent protein kinase and ATM, and suggest how ATM may signal the presence of DNA damage to p53 and other downstream effectors.\n          </jats:p>",
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