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The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles
Norman Zielke1, Silvia Querings, Carmen Rottig
1University of Cologne, Institute for Genetics, 50674 Köln, Germany.
Genes & Development
|June 19, 2008
Summary
Drosophila endoreplicating cells use Geminin to prevent DNA replication errors. Cyclin E-dependent kinase activity oscillations, regulated by the anaphase-promoting complex/cyclosome (APC/C), control Geminin levels and endocycle progression.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Endoreplication involves repeated DNA replication without cell division, leading to polyploidy.
- Cyclin E (CycE)-dependent kinase activity drives Drosophila endocycles, with high activity initiating S phase.
- Geminin normally prevents DNA re-replication in mitotic cells during S phase.
Purpose of the Study:
- To investigate the role and regulation of Geminin in Drosophila endoreplicating cells.
- To determine the mechanism controlling Geminin oscillation during the endocycle.
- To understand how DNA replication licensing is controlled in the absence of mitosis.
Main Methods:
- Analysis of Geminin protein oscillation in Drosophila salivary glands.
- Investigating the requirement of anaphase-promoting complex/cyclosome (APC/C) activity for Geminin regulation.
- Assessing the impact of APC/C inhibition on endocycle progression and Geminin stability.
Main Results:
- Geminin protein levels oscillate in endoreplicating salivary glands, peaking in S phase and decreasing post-replication.
- APC/C activity is essential for Geminin oscillation in endoreplicating cells, despite the absence of mitosis.
- Inhibition of APC/C leads to Geminin stabilization and blocks endocycle progression.
- Geminin abundance correlates with high Cyclin E-Cdk2 activity, suggesting CycE-Cdk2 inhibits APC/C-Fzr to prevent re-licensing.
Conclusions:
- Geminin oscillation, regulated by APC/C activity, is crucial for proper endocycle progression in Drosophila.
- The cell cycle machinery, including APC/C, is adapted to control DNA replication licensing even in terminally differentiating, non-mitotic cells.
- Cyclin E-Cdk2 activity likely plays a role in inhibiting APC/C-Fzr, thereby preventing DNA re-licensing during S phase of the endocycle.
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