ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex
Copyright policy )ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex
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.
- The University of Texas at Austin United States
MRE11 Homologue Protein, DNA Repair, DNA, Single-Stranded, Nuclear Proteins, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, DNA, Acid Anhydride Hydrolases, Cell Line, DNA-Binding Proteins, Enzyme Activation, DNA Repair Enzymes, Amino Acid Substitution, Mutation, Humans, Nucleic Acid Conformation, Phosphorylation, Dimerization, DNA Damage, Protein Binding
MRE11 Homologue Protein, DNA Repair, DNA, Single-Stranded, Nuclear Proteins, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, DNA, Acid Anhydride Hydrolases, Cell Line, DNA-Binding Proteins, Enzyme Activation, DNA Repair Enzymes, Amino Acid Substitution, Mutation, Humans, Nucleic Acid Conformation, Phosphorylation, Dimerization, DNA Damage, Protein Binding
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