| Title | ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. | | Author(s) | Lee JH, Paull TT | | Institution | 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. | | Source | Science 2005 Apr 22; 308(5721):551-4. | | MeSH | Amino Acid Substitution
Cell Cycle Proteins
Cell Line
DNA
DNA Damage
DNA Repair
DNA Repair Enzymes
DNA, Single-Stranded
DNA-Binding Proteins
Dimerization
Enzyme Activation
Humans
Mutation
Nuclear Proteins
Nucleic Acid Conformation
Phosphorylation
Protein Binding
Protein-Serine-Threonine Kinases
Recombinant Proteins
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Serine
Signal Transduction
Transfection
Tumor Suppressor Proteins
| | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 15790808 |
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