DOI: 10.1126/science.1108297. ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex

ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex

10.1126/science.1108297

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The ataxia-telangiectasia mutated (ATM) kinase signals the presence of DNA double-strand breaks in mammalian cells by phosphorylating proteins that initiate cell-cycle arrest, apoptosis, and DNA repair. We show that the Mre11-Rad50-Nbs1 (MRN) complex acts as a double-strand break sensor for ATM and recruits ATM to broken DNA molecules. Inactive ATM dimers were activated in vitro with DNA in the presence of MRN, leading to phosphorylation of the downstream cellular targets p53 and Chk2. ATM autophosphorylation was not required for monomerization of ATM by MRN. The unwinding of DNA ends by MRN was essential for ATM stimulation, which is consistent with the central role of single-stranded DNA as an evolutionarily conserved signal for DNA damage.

Bibliography

Lee, J.-H., & Paull, T. T. (2005). ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex. Science, 308(5721), 551â554.

Authors 2

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

References 21 Referenced 1,127

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Materials and methods are available as supporting material on Science Online.
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Molecular interaction data have been deposited in the Biomolecular Interaction Network Database (BIND) with accession codes 216020 to 216045. We thank M. Kastan and R. Abraham for expression constructs; D. Ramsden M. Gellert and M. O'Dea for Rag1/Rag2 protein; S. Stevens for technical advice; members of the Paull lab for their help; and R. Rothstein for a helpful word. This work was supported by NIH (grant CA094008) and by the American Cancer Society (grant RSG-04-173-01-CCG).

Dates

Type	When
Created	20 years, 5 months ago (March 24, 2005, 8:35 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 11:34 p.m.)
Indexed	2 days, 4 hours ago (Aug. 24, 2025, 6:51 p.m.)
Issued	20 years, 4 months ago (April 22, 2005)
Published	20 years, 4 months ago (April 22, 2005)
Published Print	20 years, 4 months ago (April 22, 2005)

Funders 0

None

BibTeX

@article{Lee_2005, title={ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex}, volume={308}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1108297}, DOI={10.1126/science.1108297}, number={5721}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Lee, Ji-Hoon and Paull, Tanya T.}, year={2005}, month=apr, pages={551–554} }

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