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Reference - PMID:18158900 - A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast centromeres.

Reference summary

PubMed ID
PMID:18158900
Title
A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast centromeres.
Authors
Dunleavy EM, Pidoux AL, Monet M, Bonilla C, Richardson W, Hamilton GL, Ekwall K, McLaughlin PJ, Allshire RC
Citation
Mol Cell 2007 Dec 28;28(6):1029-44
Publication year
2007
Abstract
A defining feature of centromeres is the presence of the histone H3 variant CENP-A(Cnp1). It is not known how CENP-A(Cnp1) is specifically delivered to, and assembled into, centromeric chromatin. Through a screen for factors involved in kinetochore integrity in fission yeast, we identified Sim3. Sim3 is homologous to known histone binding proteins NASP(Human) and N1/N2(Xenopus) and aligns with Hif1(S. cerevisiae), defining the SHNi-TPR family. Sim3 is distributed throughout the nucleoplasm, yet it associates with CENP-A(Cnp1) and also binds H3. Cells defective in Sim3 function have reduced levels of CENP-A(Cnp1) at centromeres (and increased H3) and display chromosome segregation defects. Sim3 is required to allow newly synthesized CENP-A(Cnp1) to accumulate at centromeres in S and G2 phase-arrested cells in a replication-independent mechanism. We propose that one function of Sim3 is to act as an escort that hands off CENP-A(Cnp1) to chromatin assembly factors, allowing its incorporation into centromeric chromatin.

Annotation

GO biological process

GO:0034080 - CENP-A containing chromatin assembly

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GO cellular component

GO:0005654 - nucleoplasm

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GO molecular function

GO:0140713 - histone chaperone activity

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Single locus phenotype

FYPO:0000214 - abnormal mitotic chromosome condensation

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FYPO:0001270 - complete but unequal mitotic sister chromatid segregation

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FYPO:0000080 - decreased cell population growth at low temperature

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FYPO:0003217 - decreased chromatin silencing at centromere central core

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FYPO:0000450 - decreased protein localization to centromere during vegetative growth

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FYPO:0001355 - decreased vegetative cell population growth

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FYPO:0000228 - lagging mitotic chromosomes

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FYPO:0004742 - normal chromatin silencing at centromere outer repeat

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FYPO:0003555 - normal chromatin silencing at subtelomere

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FYPO:0001796 - protein mislocalized to centromere

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Orthologs