Document Detail


The Saccharomyces cerevisiae anaphase-promoting complex interacts with multiple histone-modifying enzymes to regulate cell cycle progression.
MedLine Citation:
PMID:  20709786     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The anaphase-promoting complex (APC), a large evolutionarily conserved ubiquitin ligase complex, regulates cell cycle progression through mitosis and G(1). Here, we present data suggesting that APC-dependent cell cycle progression relies on a specific set of posttranslational histone-modifying enzymes. Multiple APC subunit mutants were impaired in total and modified histone H3 protein content. Acetylated H3K56 (H3K56(Ac)) levels were as reduced as those of total H3, indicating that loading histones with H3K56(Ac) is unaffected in APC mutants. However, under restrictive conditions, H3K9(Ac) and dimethylated H3K79 (H3K79(me2)) levels were more greatly reduced than those of total H3. In a screen for histone acetyltransferase (HAT) and histone deacetylase (HDAC) mutants that genetically interact with the apc5(CA) (chromatin assembly) mutant, we found that deletion of GCN5 or ELP3 severely hampered apc5(CA) temperature-sensitive (ts) growth. Further analyses showed that (i) the elp3Δ gcn5Δ double mutant ts defect was epistatic to that observed in apc5(CA) cells; (ii) gcn5Δ and elp3Δ mutants accumulate in mitosis; and (iii) turnover of the APC substrate Clb2 is not impaired in elp3Δ gcn5Δ cells. Increased expression of ELP3 and GCN5, as well as genes encoding the HAT Rtt109 and the chromatin assembly factors Msi1 and Asf1, suppressed apc5(CA) defects, while increased APC5 expression partially suppressed elp3Δ gcn5Δ growth defects. Finally, we demonstrate that Gcn5 is unstable during G(1) and following G(1) arrest and is stabilized in APC mutants. We present our working model in which Elp3/Gcn5 and the APC work together to facilitate passage through mitosis and G(1). To progress into S, we propose that at least Gcn5 must then be targeted for degradation in an APC-dependent fashion.
Authors:
Emma L Turner; Mackenzie E Malo; Marnie G Pisclevich; Megan D Dash; Gerald F Davies; Terra G Arnason; Troy A A Harkness
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-13
Journal Detail:
Title:  Eukaryotic cell     Volume:  9     ISSN:  1535-9786     ISO Abbreviation:  Eukaryotic Cell     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2011-01-28     Revised Date:  2011-07-27    
Medline Journal Info:
Nlm Unique ID:  101130731     Medline TA:  Eukaryot Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1418-31     Citation Subset:  IM    
Affiliation:
Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Canada.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle / genetics,  physiology
Chromatin Assembly and Disassembly
Gene Expression Regulation, Fungal*
Histone Acetyltransferases / genetics,  metabolism*
Histones / metabolism*
Mitosis / physiology*
Saccharomyces cerevisiae / cytology*,  genetics,  metabolism
Saccharomyces cerevisiae Proteins / genetics,  metabolism*
Ubiquitin-Protein Ligase Complexes / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Histones; 0/Saccharomyces cerevisiae Proteins; EC 2.3.1.48/Elp3 protein, S cerevisiae; EC 2.3.1.48/GCN5 protein, S cerevisiae; EC 2.3.1.48/Histone Acetyltransferases; EC 6.3.2.19/Ubiquitin-Protein Ligase Complexes; EC 6.3.2.19/anaphase-promoting complex
Comments/Corrections

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