This study reports an unusual ploidy-specific response to replication stress presented by a defective minichromosome maintenance (MCM) helicase allele in yeast. The corresponding mouse allele, Mcm4(Chaos3), predisposes mice to mammary gland tumors. While mcm4(Chaos3) causes replication stress in both haploid and diploid yeast, only diploid mutants exhibit G2/M delay, severe genetic instability (GIN), and reduced viability. These different outcomes are associated with distinct repair pathways adopted in haploid and diploid mutants. Haploid mutants use the Rad6-dependent pathways that resume stalled forks, whereas the diploid mutants use the Rad52- and MRX-dependent pathways that repair double strand breaks. The repair pathway choice is irreversible and not regulated by the availability of repair enzymes. This ploidy effect is independent of mating type heterozygosity and not further enhanced by increasing ploidy. In summary, a defective MCM helicase causes GIN only in particular cell types. In response to replication stress, early events associated with ploidy dictate the repair pathway choice. This study uncovers a fundamental difference between haplophase and diplophase in the maintenance of genome integrity.
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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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Evidence ID | Analyze ID | File | Description |
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