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

Nakayama, J., Xiao, G., Noma, K., Malikzay, A., Bjerling, P., Ekwall, K., Kobayashi, R., Grewal, S. I. (June 2003) Alp13, an MRG family protein, is a component of fission yeast Clr6 histone deacetylase required for genomic integrity. Embo Journal, 22 (11). pp. 2776-87. ISSN 0261-4189

URL: http://www.ncbi.nlm.nih.gov/pubmed/12773392
DOI: 10.1093/emboj/cdg248

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.

Item Type: Paper
Uncontrolled Keywords: Acetylation Amino Acid Sequence Cell Aging Cell Cycle Proteins/ chemistry/genetics/ metabolism 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
Subjects: bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > histone deacetylase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
organism description > yeast
CSHL Authors:
Communities: CSHL labs > Grewal lab
CSHL labs > Kobayashi lab
Depositing User: Matt Covey
Date: 2 June 2003
Date Deposited: 27 Jun 2013 15:04
Last Modified: 27 Jun 2013 15:04
PMCID: PMC156745
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27932

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