PT - JOURNAL ARTICLE AU - Lee, Ji-Hoon AU - Paull, Tanya T. TI - ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex AID - 10.1126/science.1108297 DP - 2005 Apr 22 TA - Science PG - 551--554 VI - 308 IP - 5721 4099 - http://science.sciencemag.org/content/308/5721/551.short 4100 - http://science.sciencemag.org/content/308/5721/551.full SO - Science2005 Apr 22; 308 AB - 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.