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A Cdc2 dependent checkpoint maintains diploidy in Drosophila
1National Institute of Genetics, Mishima, Shizuoka-ken, Japan.
Development (Cambridge, England)
|April 1, 1996
Summary
The escargot gene maintains G2/M cyclin-dependent kinase (cdk) levels to prevent DNA replication during G2 phase. Loss of escargot function leads to G2 cells entering an endocycle, bypassing normal cell cycle checkpoints.
Area of Science:
- Cell Biology
- Genetics
- Developmental Biology
Background:
- DNA replication is tightly regulated, with checkpoints preventing its occurrence in G2 phase.
- The G2/M checkpoint ensures proper cell cycle progression and genomic integrity.
Purpose of the Study:
- To investigate the mechanism of G2 checkpoint control.
- To elucidate the roles of the escargot and Dmcdc2 genes in regulating DNA replication and cell cycle progression in Drosophila.
Main Methods:
- Genetic analysis of escargot and Dmcdc2 mutants in Drosophila.
- Observation of cell cycle progression in diploid imaginal cells, salivary glands, central nervous system, and abdominal histoblasts.
- Assay of Cyclin A levels in escargot mutants.
Main Results:
- Loss of escargot function caused G2-arrested diploid cells to lose Cyclin A and enter an endocycle.
- escargot genetically interacted with Dmcdc2, a G2/M cdk catalytic subunit.
- Mutations in Dmcdc2 phenocopied escargot mutants, leading to endocycle entry and polytene chromosome formation.
- Mitotically quiescent cells required Dmcdc2 to maintain diploidy.
Conclusions:
- The escargot gene is essential for maintaining high G2/M cdk levels in G2 phase.
- This high G2/M cdk activity actively inhibits entry into S phase, thus enforcing the G2 checkpoint.
- The inhibitory activity of G2/M cdk on DNA replication is separable from its role in promoting mitosis.