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Description

A cell-permeable pyrimidinone compound that inhibits the exonuclease activity of Mre11, component of the MRN (Mre11-Rad50-Nbs1) complex, and prevents MRN-mediated activation of dimeric ATM (IC50 = 12 µ,M) in cell-free p53 Ser15 phosphorylation assays, while exhibiting little effect against MRN-independent ATM activation in the presence of high DSBs (DNA double strain breaks) or the activity of activated monomeric ATM. Mirin is shown to cause an increase of G2 population in exponentially growing TOSA4 cultures (~1.6-fold at 50 µ,M) and dramatically increase mitotic cell polulation (~10-fold at 25 µ,M) after irradiation of G2 phase U2OS cultures by preventing IR-induced G2/M checkpoint. Mirin exhibits no inhibitory activity against Rad50-associated adenylate kinase or Exonulease III.