RT Journal Article
SR Electronic
T1 ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex
JF Science
JO Science
FD American Association for the Advancement of Science
SP 551
OP 554
DO 10.1126/science.1108297
VO 308
IS 5721
A1 Lee, Ji-Hoon
A1 Paull, Tanya T.
YR 2005
UL http://science.sciencemag.org/content/308/5721/551.abstract
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.