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Fig. 7. HDAC inhibition facilitates sister chromatid separation in S. pombe mutants. (A) ts mutants of S. pombe separase Cut1 and securin Cut2 were suppressed by TSA. cut1-206, cut1-T693, cut1-21 and cut2-364 growing exponentially at 26°C were spotted on YPD plates lacking or containing TSA (12.5 µg/ml), and then incubated at 26, 30, 33 and 36°C. (B) Wild type, cut9-665,
pka1 and cut9-665
pka1 mutants grown exponentially were diluted and spotted on YPD plates lacking or containing TSA (12.5 µg/m). (C) cut9-665 and cut9-665
mad2 stains were spotted as B. cut9-665
mad2 double mutants grew better than the cut9-665 single mutants; however, the temperature sensitivities were further suppressed in the presence of TSA. (D) Results presented in the present study are summarized. Clr6, Clr3 and Hos2 are three HDACs that are sensitive to TSA. Clr6 inhibition facilitates the assembly of APC/C ubiquitin ligase complex in the mutant cells. Inhibition of Clr3 and Hos2 deteriorates chromatin loading of cohesin complex through Mis4 destablisation. In both cases, sister chromatid separation is promoted.