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Reference - PMID:41786187 - Shugoshin holds the potential to inhibit APC/C and thereby prevents separase activation.

Reference summary

PubMed ID
PMID:41786187
Title
Shugoshin holds the potential to inhibit APC/C and thereby prevents separase activation.
Authors
Zhang K, Guo S, Sun L, Hou H, Watanabe Y
Citation
Int J Biol Macromol 2026 Mar 03;:151175
Publication year
2026
Abstract
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 demonstrate that ectopic expression of Sgo1 causes chromosome segregation errors during mitosis, especially in cut1-206 separase mutant cells. However, Sgo1D-box mutant does not exhibit this effect in cut1-206 cells. Our molecular genetic analyses suggest that the Sgo1 D-box directly binds Slp1/CDC20, inhibiting APC/C-dependent separase activation and consequently preventing Rad21 cohesin cleavage. 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.

Annotation

Multi-locus phenotype

FYPO:0000029 - abnormal chromosome segregation

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FYPO:0000141 - abnormal mitotic sister chromatid segregation

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FYPO:0006315 - abolished homologous chromosome segregation

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FYPO:0001946 - abolished mitotic sister chromatid separation

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FYPO:0000460 - decreased mitotic centromeric sister chromatid cohesion

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FYPO:0002061 - inviable vegetative cell population

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FYPO:0001357 - normal vegetative cell population growth

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Protein sequence feature

SO:0001805 - destruction_box

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Single locus phenotype

FYPO:0007104 - abnormal homologous chromosome arm segregation

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FYPO:0000141 - abnormal mitotic sister chromatid segregation

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FYPO:0007649 - abolished protein localization to pericentric heterochromatin during meiosis II

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FYPO:0000460 - decreased mitotic centromeric sister chromatid cohesion

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FYPO:0001645 - decreased protein-protein interaction

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FYPO:0006531 - delayed onset of protein degradation during meiosis

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FYPO:0003182 - sister chromatid nondisjunction at meiosis II

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