Mirin

Description: Mirin is a potent inhibitor of the MRN (Mre11 / Rad50 / Nbs1) complex and Ataxia Telangiectasia-Mutated (ATM) protein kinase. The Ataxia Telangiectasia-Mutated (ATM) protein kinase is recruited to sites of double-strand DNA breaks by the Mre11/Rad50/Nbs1 (MRN) complex, which also facilitates ATM monomerization and activation. MRN exists in at least two distinct conformational states, dependent on ATP binding and hydrolysis by the Rad50 protein. Mre11 nuclease activity is dispensable, although some mutations in the Mre11 catalytic domain block ATM activation independent of nuclease function, as does the mirin compound. Addition of the Mre11 inhibitor mirin to egg extracts and mammalian cells reduces RCC1 association with mitotic chromosomes. Thus, the MRN-CtIP pathway contributes to Ran-dependent mitotic spindle assembly by modulating RCC1 chromosome association.

References: Mol Cell. 2013 Mar 28; 49(6):1097-107; J Biol Chem. 2013 May 3; 288(18):12840-51.