Mirin

Mirin is a small-molecule inhibitor of MRN (Mre11, Rad50, and Nbs1) complex. Target: in vitro: Mirin was shown to block Mre11 exonuclease activity and MRN-dependent ATM activation, and to inhibit the ionizing radiation-induced G2/M checkpoint and homologous recombination in mammalian cells. Mirin inhibition of ATM activation is independent of Mre11 nuclease inhibition since the M(HN)RN and M(HL/DV)RN mutant complexes are inhibited equivalently to the wild-type enzyme despite the fact that they are nuclease-deficient. The effects of Mirin have been ascribed to its effects on Mre11 nuclease activity, but as we show here, Mirin is inhibitory of MRN function independent of the nuclease activity of the complex. [2] Addition of the Mre11 inhibitor Mirin to egg extracts and mammalian cells reduces RCC1 association with mitotic chromosomes. HeLa cells expressing Histone H2B-EYFP were treated with Mirin (25 or 50 μM), and mitotic progression was immediately monitored using live cell imaging. Although Mirin-treated cells were able to congress chromosomes to the metaphase plate with similar kinetics as untreated cells, a significant fraction of Mirin-treated cells paused for extended periods of time in a metaphase-like stage without anaphase onset . [1]

References:
[1]. Rozier L, et al. The MRN-CtIP pathway is required for metaphase chromosome alignment. Mol Cell. 2013 Mar 28;49(6):1097-107. [2]. Lee JH, et al. Ataxia telangiectasia-mutated (ATM) kinase activity is regulated by ATP-driven conformational changes in the Mre11/Rad50/Nbs1 (MRN) complex. J Biol Chem. 2013 May 3;288(18):12840-51. [3]. Garner KM, et al. Corrected structure of Mirin, a small-molecule inhibitor of the Mre11-Rad50-Nbs1 complex. Nat Chem Biol. 2009 Mar;5(3):129-30.

Formation of ethyl ferulate by rice koji enzyme in sake and mirin mash conditions.[Pubmed:23597918]

J Biosci Bioeng. 2013 Aug;116(2):209-13.

Formation mechanism of ethyl ferulate (EF) in sake and Mirin mash conditions was investigated to understand EF level control in the manufacturing process. Rice koji formed EF from ferulic acid (FA) and ethanol and decomposed EF to FA. This did not occur in sake yeast and chemical esterification was rare. Esterification of FA and hydrolysis of EF by rice koji might be due to feruloyl esterase(s). The rice koji enzyme showed normal Michaelis-Menten kinetics for FA in ethyl esterification and for EF in hydrolysis, but not for ethanol in the esterification reaction. Substrate specificity of the rice koji enzyme for hydroxycinnamic acids suggested that the main enzyme involved might be similar to type A feruloyl esterase. We studied the rice koji enzyme properties, short-term digestion of steamed rice grains with exogenous ethanol and small scale Mirin making with pH adjustment. Our results suggested differences in the esterification and hydrolysis properties of the enzyme, in particular, different pH dependencies and different behaviors under high ethanol conditions; these factors might cause the differing EF levels in sake and Mirin mashes.

Mirin: identifying microRNA regulatory modules in protein-protein interaction networks.[Pubmed:24794934]

Bioinformatics. 2014 Sep 1;30(17):2527-8.

UNLABELLED: Exploring microRNA (miRNA) regulations and protein-protein interactions could reveal the molecular mechanisms responsible for complex biological processes. Mirin is a web-based application suitable for identifying functional modules from protein-protein interaction networks regulated by aberrant miRNAs under user-defined biological conditions such as cancers. The analysis involves combining miRNA regulations, protein-protein interactions between target genes, as well as mRNA and miRNA expression profiles provided by users. Mirin has successfully uncovered oncomirs and their regulatory networks in various cancers, such as gastric and breast cancer. AVAILABILITY AND IMPLEMENTATION: Mirin is freely available at http://Mirin.ym.edu.tw/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Aroma compounds in Japanese sweet rice wine (Mirin) screened by aroma extract dilution analysis (AEDA).[Pubmed:25391446]

Biosci Biotechnol Biochem. 2015;79(3):484-7.

Thirty-nine key aroma compounds were newly identified or tentatively identified in the aroma concentrate of Japanese sweet rice wine (Mirin) by an aroma extract dilution analysis technique based on the 68 detected peaks. Among them, 3-(methylthio)propanal, 3-hydroxy-4,5-dimethyl-2(5H)-furanone, 3-methylbutanoic acid, 2-methylbutanoic acid, and 2-methoxy-4-vinylphenol were detected with the highest FD factors in this study.

A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex.[Pubmed:18176557]

Nat Chem Biol. 2008 Feb;4(2):119-25.

The MRN (Mre11-Rad50-Nbs1)-ATM (ataxia-telangiectasia mutated) pathway is essential for sensing and signaling from DNA double-strand breaks. The MRN complex acts as a DNA damage sensor, maintains genome stability during DNA replication, promotes homology-dependent DNA repair and activates ATM. MRN is essential for cell viability, which has limited functional studies of the complex. Small-molecule inhibitors of MRN could circumvent this experimental limitation and could also be used as cellular radio- and chemosensitization compounds. Using cell-free systems that recapitulate faithfully the MRN-ATM signaling pathway, we designed a forward chemical genetic screen to identify inhibitors of the pathway, and we isolated 6-(4-hydroxyphenyl)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone (Mirin, 1) as an inhibitor of MRN. Mirin prevents MRN-dependent activation of ATM without affecting ATM protein kinase activity, and it inhibits Mre11-associated exonuclease activity. Consistent with its ability to target the MRN complex, Mirin abolishes the G2/M checkpoint and homology-dependent repair in mammalian cells.