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. 2005 Apr 22;308(5721):551-4.
doi: 10.1126/science.1108297. Epub 2005 Mar 24.

ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex

Ji-Hoon Lee  1 , Tanya T Paull
Affiliations

ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex

Ji-Hoon Lee et al. Science. .

Erratum in

  • Science. 2005 Jun 24;308(5730):1870

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.

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