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PMID: 12773392 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The EMBO journal ·Vol. 22 ·No. 11 ·2003-06-02 ·Pages 2776-87

Nakayama J, Xiao G, Noma K, Malikzay A, Bjerling P, Ekwall K, Kobayashi R, Grewal SI

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.

MeSH Terms
Acetylation Amino Acid Sequence Cell Cycle Proteins/chemistry,genetics,metabolism Cellular Senescence Conserved Sequence Gene Deletion Genome, Fungal Histone Deacetylases/chemistry,genetics,metabolism Histones/chemistry,metabolism Humans Mitosis Molecular Sequence Data Mutation Peptide Fragments/genetics Schizosaccharomyces/cytology,genetics,metabolism Schizosaccharomyces pombe Proteins/chemistry,genetics,metabolism Serine/chemistry
Chemicals
Alp13 protein, S pombe Cell Cycle Proteins Clr6 protein, S pombe Histones Peptide Fragments Schizosaccharomyces pombe Proteins Serine Histone Deacetylases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Nakayama Jun-Ichi
Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, NY 11724, USA.
Xiao Guoping
Noma Ken-Ichi
Malikzay Asra
Bjerling Pernilla
Ekwall Karl
Kobayashi Ryuji
Grewal Shiv I S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg248
Published
2003-06-02
Pages
2776-87
Language
English
Region
England
NLM ID
8208664
PMCID
PMC156745
Subset
IM
Grants
NIGMS NIH HHS · R01 GM059772 · United States
NIGMS NIH HHS · GM59772 · United States
External Links
PubMed source DOI: 10.1093/emboj/cdg248 PMC Full Text View journal details
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