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Reference - PMID:12773390 - The role of Ppe1/PP6 phosphatase for equal chromosome segregation in fission yeast kinetochore.

Reference summary

PubMed ID
PMID:12773390
Title
The role of Ppe1/PP6 phosphatase for equal chromosome segregation in fission yeast kinetochore.
Authors
Goshima G, Iwasaki O, Obuse C, Yanagida M
Citation
EMBO J 2003 Jun 02;22(11):2752-63
Publication year
2003
Abstract
Mis12 is a kinetochore protein essential for equal chromosome segregation and is evolutionarily conserved from yeast to human. In this study, we report the isolation and characterization of suppressors of the mis12 mutant in fission yeast. Our results indicate that Mis12 is negatively regulated by a highly conserved protein phosphatase Ppe1 (scSit4/dmPPV/hPP6) or its bound partner Ekc1 (scSAP), and it is positively regulated by a counteracting kinase Gsk3. Mass spectrometry analysis shows that at least two sites in Mis12 are phosphorylated. This mechanism of suppression occurs at the level of localization recovery of Mis12 to the kinetochore chromatin. Consistently, Mis12 and a subpopulation of Ppe1/Ekc1 were found to behave like non-histone-type chromatin-associating proteins in the chromatin fractionation assay. Mutant analysis of Ppe1 and Ekc1 revealed that they are important for faithful chromosome segregation, as the mutants exhibited unequal chromosome segregation similar to mis12 in the presence of a low concentration of tubulin poison. Ppe1/PP6 directly or indirectly modulates kinetochore chromatin protein Mis12 to ensure progression into normal anaphase.

Annotation

GO biological process

GO:1905560 - negative regulation of kinetochore assembly

Genes:

GO:1905561 - positive regulation of kinetochore assembly

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GO cellular component

GO:0000785 - chromatin

Genes:

GO:0005654 - nucleoplasm

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GO:0008287 - protein serine/threonine phosphatase complex

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GO molecular function

GO:0005515 - protein binding

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GO:0072542 - protein phosphatase activator activity

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Modification

MOD:00046 - O-phospho-L-serine

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MOD:00047 - O-phospho-L-threonine

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Multi-locus phenotype

FYPO:0002061 - inviable vegetative cell population

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Genotypes:

FYPO:0002901 - normal protein localization to kinetochore during vegetative growth

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FYPO:0000091 - sensitive to thiabendazole

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FYPO:0002060 - viable vegetative cell population

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Single locus phenotype

FYPO:0001269 - abolished protein localization to kinetochore during vegetative growth

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Genotypes:

FYPO:0002061 - inviable vegetative cell population

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FYPO:0000964 - normal growth on thiabendazole

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FYPO:0000113 - sensitive to staurosporine

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Genotypes:

FYPO:0000091 - sensitive to thiabendazole

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Genotypes:

FYPO:0003241 - unequal mitotic sister chromatid segregation

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FYPO:0002106 - viable stubby vegetative cell

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