DOI: 10.1126/science.1091496. Direct Activation of the ATM Protein Kinase by the Mre11/Rad50/Nbs1 Complex

Direct Activation of the ATM Protein Kinase by the Mre11/Rad50/Nbs1 Complex

10.1126/science.1091496

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The complex containing the Mre11, Rad50, and Nbs1 proteins (MRN) is essential for the cellular response to DNA double-strand breaks, integrating DNA repair with the activation of checkpoint signaling through the protein kinase ATM (ataxia telangiectasia mutated). We demonstrate that MRN stimulates the kinase activity of ATM in vitro toward its substrates p53, Chk2, and histone H2AX. MRN makes multiple contacts with ATM and appears to stimulate ATM activity by facilitating the stable binding of substrates. Phosphorylation of Nbs1 is critical for MRN stimulation of ATM activity toward Chk2, but not p53. Kinase-deficient ATM inhibits wild-type ATM phosphorylation of Chk2, consistent with the dominant-negative effect of kinase-deficient ATM in vivo.

Bibliography

Lee, J.-H., & Paull, T. T. (2004). Direct Activation of the ATM Protein Kinase by the Mre11/Rad50/Nbs1 Complex. Science, 304(5667), 93â96.

Authors 2

Ji-Hoon Lee (first)
Tanya T. Paull (additional)

References 31 Referenced 592

10.1038/nrc1011
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Materials and methods are available as supporting material on Science Online.
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We thank M. Kastan J. Huibregtse and J. Chung for expression constructs and J. Gautier for comments on the manuscript. Supported by the NIH (CA94008) and the Kimmel Cancer Research Foundation.

Dates

Type	When
Created	21 years, 4 months ago (April 1, 2004, 4:28 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 11:39 p.m.)
Indexed	11 minutes ago (Aug. 29, 2025, 9:46 a.m.)
Issued	21 years, 4 months ago (April 2, 2004)
Published	21 years, 4 months ago (April 2, 2004)
Published Print	21 years, 4 months ago (April 2, 2004)

Funders 0

None

BibTeX

@article{Lee_2004, title={Direct Activation of the ATM Protein Kinase by the Mre11/Rad50/Nbs1 Complex}, volume={304}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1091496}, DOI={10.1126/science.1091496}, number={5667}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Lee, Ji-Hoon and Paull, Tanya T.}, year={2004}, month=apr, pages={93–96} }

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