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The Saccharomyces cerevisiae anaphase-promoting complex interacts with multiple histone-modifying enzymes to regulate
Emma L Turner1, Mackenzie E Malo, Marnie G Pisclevich
1Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Canada.
Eukaryotic Cell
|August 17, 2010
Summary
The anaphase-promoting complex (APC) controls cell division by interacting with histone-modifying enzymes. APC mutants show reduced histone levels, impacting cell cycle progression and mitosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Epigenetics
Background:
- The anaphase-promoting complex (APC) is a crucial ubiquitin ligase regulating cell cycle progression through mitosis and G1.
- Histone modifications play a significant role in regulating gene expression and chromatin structure during the cell cycle.
Purpose of the Study:
- To investigate the relationship between APC function and posttranslational histone-modifying enzymes.
- To identify specific histone-modifying enzymes involved in APC-dependent cell cycle progression.
- To elucidate the roles of GCN5 and ELP3 in APC-mediated regulation.
Main Methods:
- Analysis of APC subunit mutants for total and modified histone H3 protein levels.
- Genetic interaction screening of histone acetyltransferase (HAT) and histone deacetylase (HDAC) mutants with an apc5(CA) mutant.
- Temperature-sensitive growth assays, epistasis analysis, and protein stability studies.
Main Results:
- APC mutants exhibited reduced levels of total H3, H3K9(Ac), and H3K79(me2).
- Deletion of GCN5 or ELP3 severely impaired the growth of apc5(CA) mutants and caused mitotic accumulation.
- Gcn5 protein was found to be unstable during G1 and stabilized in APC mutants, suggesting APC-dependent regulation of Gcn5 stability.
Conclusions:
- APC-dependent cell cycle progression relies on specific histone-modifying enzymes, particularly GCN5 and ELP3.
- The APC and Elp3/Gcn5 complex cooperate to facilitate passage through mitosis and G1.
- Gcn5 degradation, regulated by the APC, is proposed to be essential for progression into the S phase.
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