Mutations arising during times of cell cycle-arrest may considerably contribute to aging and cancerogenesis. Endogenous oxidative stress could be one of the major triggers for these mutations. We used Saccharomyces cerevisiae cells, arrested by starvation for the essential amino acid lysine, to study the occurrence of reactive oxygen species (ROS), abasic (AP) sites and double strand breaks (DSBs). Furthermore, we analyzed the mutation frequencies in resting wild type cells and in cells deficient for Apn1 (with an impaired base excision repair) or Dnl4 (with an inactivated non-homologous end joining (NHEJ) DSB repair pathway) by monitoring reversions of an auxotrophy-causing frameshift in the LYS2 gene. By fluorescence methods, we observed a distinct increase of ROS-affected cells in the course of starvation-induced cell cycle-arrest. In addition, we could reveal that AP sites and DSBs accumulated under these conditions. The frequency of spontaneous frameshift mutations in wild type cells was decreased to 50% upon addition of 6mM N-acetyl cysteine. However, this radical scavenger had no effect in Dnl4-deficient cells. Our results support the hypothesis that (via an active NHEJ DSB repair pathway) the incidence of spontaneous frameshift mutations in a cell cycle-arrested state is considerably governed by oxidative stress.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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