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Reference - PMID:12773392 - Alp13, an MRG family protein, is a component of fission yeast Clr6 histone deacetylase required for genomic integrity.

Reference summary

PubMed ID
PMID:12773392
Title
Alp13, an MRG family protein, is a component of fission yeast Clr6 histone deacetylase required for genomic integrity.
Authors
Nakayama J, Xiao G, Noma K, Malikzay A, Bjerling P, Ekwall K, Kobayashi R, Grewal SI
Citation
EMBO J 2003 Jun 02;22(11):2776-87
Publication year
2003
Abstract
The post-translational modifications of histones are key to the modulation of chromatin structure. Distinct patterns of modifications established by histone-modifying enzymes control diverse chromosomal processes. Here, we report the purification and molecular characterization of the fission yeast Clr6 histone deacetyl ase involved in higher order chromatin assembly. We show that a chromodomain protein Alp13, which belongs to the conserved MRG protein family linked to cellular senescence in humans, is associated with Clr6. In addition, Clr6 interacts with homologs of the mammalian transcriptional co-repressors Sin3, Pst1 and Pst2, and a WD40 repeat-containing protein, Prw1. Alp13, Pst2 and Prw1 form a stable complex with Clr6 in the nucleus. Deletion of any of these factors causes progressive loss of viability and sensitivity to DNA-damaging agents, and impairs condensation/resolution of chromosomes during mitosis. This is accompanied by hyperacetylation of histones and a reduction in histone H3 Ser10 phosphorylation, which correlates with chromosome condensation during mitosis. These results link the MRG family protein Alp13 to histone deacetylation, and suggest that Clr6 and its associated factors are essential for fundamental chromosomal events.

Annotation

GO cellular component

GO:0005634 - nucleus

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GO:0032221 - Rpd3S complex

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GO:0005730 - nucleolus

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GO molecular function

GO:0004407 - histone deacetylase activity

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GO:0031078 - histone H3K14 deacetylase activity, hydrolytic mechanism

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GO:0032129 - histone H3K9 deacetylase activity, hydrolytic mechanism

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GO:0140937 - histone H4K12 deacetylase activity, hydrolytic mechanism

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GO:0034739 - histone H4K16 deacetylase activity, hydrolytic mechanism

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Single locus phenotype

FYPO:0000141 - abnormal mitotic sister chromatid segregation

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FYPO:0005046 - abnormal mitotic sister chromatid segregation with lagging chromosomes, complete sister chromatid separation, and decreased rate of mitotic spindle elongation

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FYPO:0000082 - decreased cell population growth at high temperature

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FYPO:0008183 - decreased histone H3-S10 phosphorylation during vegetative growth

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FYPO:0002363 - increased histone H3 acetylation during vegetative growth

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FYPO:0005310 - increased histone H3-K14 acetylation during vegetative growth

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FYPO:0000892 - increased histone H3-K9 acetylation during vegetative growth

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FYPO:0002365 - increased histone H4 acetylation during vegetative growth

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FYPO:0007631 - increased histone H4-K12 acetylation during vegetative growth

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FYPO:0007632 - increased histone H4-K16 acetylation during vegetative growth

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FYPO:0005309 - increased histone H4-K5 acetylation during vegetative growth

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FYPO:0005308 - increased histone H4-K8 acetylation during vegetative growth

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FYPO:0000095 - sensitive to bleomycin

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FYPO:0000089 - sensitive to methyl methanesulfonate

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Genotypes:

FYPO:0000268 - sensitive to UV during vegetative growth

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