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Updated: Jun 27, 2026
Genetic Studies of Human DNA Repair Proteins Using Yeast as a Model System
Published on: March 18, 2010
The G1-S checkpoint in fission yeast is not a general DNA damage checkpoint
Marit Krohn1, Henriette C Skjølberg, Héla Soltani
1Department of Cell Biology, Institute for Cancer Research, Rikshospitalet Medical Centre, Montebello, 0310 Oslo, Norway.
Abstract:
Inhibitory mechanisms called checkpoints regulate progression of the cell cycle in the presence of DNA damage or when a previous cell-cycle event is not finished. In fission yeast exposed to ultraviolet light the G1-S transition is regulated by a novel checkpoint that depends on the Gcn2 kinase. The molecular mechanisms involved in checkpoint induction and maintenance are not known. Here we characterise the checkpoint further by exposing the cells to a variety of DNA-damaging agents. Exposure to methyl methane sulphonate and hydrogen peroxide induce phosphorylation of eIF2alpha, a known Gcn2 target, and an arrest in G1 phase. By contrast, exposure to psoralen plus long-wavelength ultraviolet light, inducing DNA adducts and crosslinks, or to ionizing radiation induce neither eIF2alpha phosphorylation nor a cell-cycle delay. We conclude that the G1-S checkpoint is not a general DNA-damage checkpoint, in contrast to the one operating at the G2-M transition. The tight correlation between eIF2alpha phosphorylation and the presence of a G1-phase delay suggests that eIF2alpha phosphorylation is required for checkpoint induction. The implications for checkpoint signalling are discussed.
Insights
Fission yeast G1-S cell cycle checkpoints are induced by specific DNA damage agents, requiring eIF2alpha phosphorylation. This checkpoint is not a general DNA damage response, unlike the G2-M transition checkpoint.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Cell cycle checkpoints prevent genomic instability by halting cell division.
- Fission yeast possess checkpoints regulating transitions like G1-S and G2-M.
- A novel G1-S checkpoint dependent on Gcn2 kinase has been identified in fission yeast.
Purpose of the Study:
- To further characterize the novel G1-S cell cycle checkpoint in fission yeast.
- To investigate the molecular mechanisms underlying checkpoint induction and maintenance.
- To determine the specificity of the G1-S checkpoint in response to various DNA-damaging agents.
Main Methods:
- Exposure of fission yeast to diverse DNA-damaging agents: methyl methane sulfonate, hydrogen peroxide, psoralen plus UV light, and ionizing radiation.
- Monitoring of eIF2alpha phosphorylation, a known Gcn2 kinase target.
- Assessment of cell cycle progression, specifically G1-phase delay.
Main Results:
- Methyl methane sulfonate and hydrogen peroxide induced eIF2alpha phosphorylation and a G1-phase arrest.
- Psoralen plus UV light and ionizing radiation did not induce eIF2alpha phosphorylation or a G1-phase delay.
- A strong correlation was observed between eIF2alpha phosphorylation and G1-phase delay.
Conclusions:
- The G1-S checkpoint in fission yeast is not a general DNA-damage checkpoint.
- eIF2alpha phosphorylation is essential for the induction of the G1-S checkpoint.
- The findings provide insights into the specific signaling pathways involved in checkpoint control.
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