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.