The MRN complex is a multifunctional nuclease that initiates DNA double-strand break repair, but also contributes to the activation of ATM-dependent damage signalling. Insight into the mechanism of how MRN and ATM interact with each other on DNA, however, is still lacking. Here we address this central question through a structural analysis of complexes of MRN and ATM with DNA, using cryo-electron microscopy. We will also interrogate and complement the structure-derived mechanisms with crosslinking mass spectrometry, biochemistry and collaborative cell-based studies in order to reveal how MRN and ATM cooperate at DNA ends.
Structural mechanism of MRN-ATM in DSB signalling and processing