Shugoshin holds the potential to inhibit APC/C and thereby prevents separase activation

Accurate chromosome segregation during mitosis and meiosis depends on shugoshin protein which localizes at the centromere of chromosomes. Sgo1, a meiosis-specific shugoshin in fission yeast, collaborates with the PP2A phosphatase enzyme to remove phosphate groups from Rec8 cohesin, thereby preventing its cleavage by separase during meiosis. Here we show that ectopic expression of Sgo1 causes chromosome segregation errors during mitosis, especially in cut1-206 separase mutant cells, but that the D-box mutant Sgo1 has no effect in cut1-206 cells. Our molecular genetic analyses suggest that the D-box of Sgo1 directly binds Slp1/CDC20 and inhibits APC/C-dependent separase activation, thereby preventing cleavage of Rad21 cohesin. In contrast, during meiosis, the Sgo1 D-box mutant makes the cut1-206 mutant more difficult to cleave Rec8 cohesin. This is because the D-box mutation increases the amount of Sgo1 protein during meiosis, thereby enhancing its canonical protective ability against Rec8 cohesin. Thus, our studies using a separase mutant have revealed that Sgo1 has multiple faces to protect coheisn.