MRN-ATM Pathway Inhibitor, Mirin

MRN-ATM Pathway Inhibitor, Mirin, has been shown to prevent Mre11-Rad50-Nbs1 (MRN)-dependent activation of ataxia-telangiectasia mutated (ATM) without affecting ATM protein kinase activity. Mirin inhibits MRN by blocking the nuclease activity of Mre11, which in turn prevents the MRN-dependent phosphorylation of histone H2AX (IC₅₀ = 66 μM). Other experiments have noted that inhibiting Mre11 also causes a reduction in the efficiency of non-homologous end joining. The MRN-ATM pathway has been reported to be essential for DNA damage detection and maintenance of genome stability during DNA replication. This pathway also promotes homology-dependent DNA repair, activates ATM, and is essential for cell viability. In vitro, mirin has been shown to induce cell-cycle arrest at the G₂ phase, override the G₂/M checkpoint, and inhibit homology-directed DNA repair.