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Reference - PMID:19965387 - Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin.

Reference summary

PubMed ID
PMID:19965387
Title
Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin.
Authors
Kawashima SA, Yamagishi Y, Honda T, Ishiguro K, Watanabe Y
Citation
Science 2010 Jan 08;327(5962):172-7
Publication year
2010
Abstract
Bub1 is a multi-task protein kinase required for proper chromosome segregation in eukaryotes. Impairment of Bub1 in humans may lead to chromosomal instability (CIN) or tumorigenesis. Yet, the primary cellular substrate of Bub1 has remained elusive. Here, we show that Bub1 phosphorylates the conserved serine 121 of histone H2A in fission yeast Schizosaccharomyces pombe. The h2a-SA mutant, in which all cellular H2A-S121 is replaced by alanine, phenocopies the bub1 kinase-dead mutant (bub1-KD) in losing the centromeric localization of shugoshin proteins. Artificial tethering of shugoshin to centromeres largely restores the h2a-SA or bub1-KD-related CIN defects, a function that is evolutionally conserved. Thus, Bub1 kinase creates a mark for shugoshin localization and the correct partitioning of chromosomes.

Annotation

GO biological process

GO:0045143 - homologous chromosome segregation

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GO cellular component

GO:0034506 - chromosome, centromeric core domain

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GO:0099115 - chromosome, subtelomeric region

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GO:0031934 - mating-type region heterochromatin

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GO:0072687 - meiotic spindle

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GO:0072686 - mitotic spindle

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GO:0005721 - pericentric heterochromatin

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GO molecular function

GO:0140463 - chromatin-protein adaptor activity

Genes:

GO:0072371 - histone H2AS121 kinase activity

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Modification

MOD:00046 - O-phospho-L-serine

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Multi-locus phenotype

FYPO:0001093 - abolished chromatin binding

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Genotypes:

FYPO:0004318 - abolished mitotic spindle assembly checkpoint

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Genotypes:

FYPO:0006455 - abolished protein localization to meiotic spindle during meiosis I

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Genotypes:

FYPO:0006456 - abolished protein localization to meiotic spindle during meiosis II

Genes:

Genotypes:

FYPO:0002033 - abolished protein phosphorylation during vegetative growth

Genes:

Genotypes:

FYPO:0006423 - decreased meiotic sister chromatid cohesion at centromere during meiosis I

Genes:

Genotypes:

FYPO:0002825 - decreased protein localization to mitotic spindle

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Genotypes:

FYPO:0002061 - inviable vegetative cell population

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Genotypes:

FYPO:0000228 - lagging mitotic chromosomes

Genes:

Genotypes:

FYPO:0001164 - normal growth on glucose carbon source

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Genotypes:

FYPO:0000091 - sensitive to thiabendazole

Genes:

Genotypes:

FYPO:0003182 - sister chromatid nondisjunction at meiosis II

Genes:

Genotypes:

FYPO:0005634 - sister kinetochore dissociation in meiotic metaphase I with equational sister chromatid segregation in meiosis I

Genes:

Genotypes:

FYPO:0002060 - viable vegetative cell population

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Genotypes:

Single locus phenotype

FYPO:0001093 - abolished chromatin binding

Genes:

Genotypes:

FYPO:0004318 - abolished mitotic spindle assembly checkpoint

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Genotypes:

FYPO:0001384 - abolished protein kinase activity

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Genotypes:

FYPO:0006457 - abolished protein localization to centromere central core during meiosis I

Genes:

Genotypes:

FYPO:0006455 - abolished protein localization to meiotic spindle during meiosis I

Genes:

Genotypes:

FYPO:0006456 - abolished protein localization to meiotic spindle during meiosis II

Genes:

Genotypes:

FYPO:0002033 - abolished protein phosphorylation during vegetative growth

Genes:

Genotypes:

FYPO:0002577 - decreased chromatin binding

Genes:

Genotypes:

FYPO:0006423 - decreased meiotic sister chromatid cohesion at centromere during meiosis I

Genes:

Genotypes:

FYPO:0002825 - decreased protein localization to mitotic spindle

Genes:

Genotypes:

FYPO:0006460 - increased histone H2A phosphorylation at protein coding gene during meiosis I

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Genotypes:

FYPO:0006462 - increased histone H2A phosphorylation at silent mating-type cassette during meiosis I

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Genotypes:

FYPO:0006461 - increased histone H2A phosphorylation at telomere during meiosis I

Genes:

Genotypes:

FYPO:0000228 - lagging mitotic chromosomes

Genes:

Genotypes:

FYPO:0001164 - normal growth on glucose carbon source

Genes:

Genotypes:

FYPO:0000091 - sensitive to thiabendazole

Genes:

Genotypes:

FYPO:0003182 - sister chromatid nondisjunction at meiosis II

Genes:

Genotypes:

FYPO:0005634 - sister kinetochore dissociation in meiotic metaphase I with equational sister chromatid segregation in meiosis I

Genes:

Genotypes: