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The ATM protein kinase plays a central role in signaling the presence of DNA double-strand breaks (DSBs) 3 in eukaryotic cells. Activation of ATM occurs very rapidly, within a few minutes of DNA break incidence, and is dependent on the Mre11/Rad50/Nbs1 (MRN) complex for its recruitment to sites of DNA damage. MRN also functions to promote a transition in ATM conformation from an inactive dimeric form to an active monomeric form, and increases the affinity of ATM for its substrates.The MRN complex is a large, multifunctional protein assembly that possesses endo-and exonucleolytic activity through the Mre11 component and ATP binding, hydrolysis, and adenylate kinase activity through the Rad50 component. Mre11/Rad50 (MR) complexes in prokaryotes and MRN complexes in eukaryotes are important for DNA double-strand break recognition and repair.