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Reference - PMID:12719471 - Sim4: a novel fission yeast kinetochore protein required for centromeric silencing and chromosome segregation.

Reference summary

PubMed ID
PMID:12719471
Title
Sim4: a novel fission yeast kinetochore protein required for centromeric silencing and chromosome segregation.
Authors
Pidoux AL, Richardson W, Allshire RC
Citation
J Cell Biol 2003 Apr 28;161(2):295-307
Publication year
2003
Abstract
Fission yeast centromeres are composed of two domains: the central core and the outer repeats. Although both regions are required for full centromere function, the central core has a distinct chromatin structure and is likely to underlie the kinetochore itself, as it is associated with centromere-specific proteins. Genes placed within either region are transcriptionally silenced, reflecting the formation of a functional kinetochore complex and flanking centromeric heterochromatin. Here, transcriptional silencing was exploited to identify components involved in central core silencing and kinetochore assembly or structure. The resulting sim (silencing in the middle of the centromere) mutants display severe chromosome segregation defects. sim2+ encodes a known kinetochore protein, the centromere-specific histone H3 variant Cnp1CENP-A. sim4+ encodes a novel essential coiled-coil protein, which is specifically associated with the central core region and is required for the unusual chromatin structure of this region. Sim4 coimmunoprecipitates with the central core component Mis6 and, like Mis6, affects Cnp1CENP-A association with the central domain. Functional Mis6 is required for Sim4 localization at the kinetochore. Our analyses illustrate the fundamental link between silencing, chromatin structure, and kinetochore function, and establish defective silencing as a powerful approach for identifying proteins required to build a functional kinetochore.

Annotation

GO cellular component

GO:0000939 - inner kinetochore

Genes:

GO:0031511 - Mis6-Sim4 complex

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Single locus phenotype

FYPO:0004308 - abnormal CENP-A containing chromatin organization

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Genotypes:

FYPO:0001978 - bent mitotic spindle

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Genotypes:

FYPO:0001270 - complete but unequal mitotic sister chromatid segregation

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Genotypes:

FYPO:0003740 - decreased CENP-A containing chromatin assembly

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Genotypes:

FYPO:0003217 - decreased chromatin silencing at centromere central core

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Genotypes:

FYPO:0002902 - decreased protein localization to kinetochore during vegetative growth

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FYPO:0002430 - inviable after spore germination, multiple cell divisions

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FYPO:0002061 - inviable vegetative cell population

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FYPO:0000228 - lagging mitotic chromosomes

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Genotypes:

FYPO:0004307 - long mitotic spindle during metaphase

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Genotypes:

FYPO:0000091 - sensitive to thiabendazole

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Genotypes:

FYPO:0000732 - short bipolar mitotic spindle

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