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      ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex.

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          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.

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          Author and article information

          Journal
          Science
          Science (New York, N.Y.)
          American Association for the Advancement of Science (AAAS)
          1095-9203
          0036-8075
          Apr 22 2005
          : 308
          : 5721
          Affiliations
          [1 ] Department of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, 1 University Station, A4800, Austin, TX 78712, USA.
          Article
          1108297
          10.1126/science.1108297
          15790808
          c24bfcf5-d297-4ed1-a011-d448690a552a
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