Genomic instability drivers of senescence and carcinogenesis. The ribosomal RNA gene (rDNA) locus in budding yeast provides an excellent model to study these processes. Because of its highly repetitive structure and the gene amplification system that maintains its copy number, rDNA represents one of the most unstable regions in the genome. Here, we demonstrate that the integrity of rDNA transcription is essential for maintaining genomic stability and lifespan. Loss of Paf1, an elongation factor associated with RNA polymerase, reduces rDNA transcription, stability, and lifespan. In paf1 mutants, R-loops accumulate within the rDNA, generating single-stranded regions prone to breakage. This triggers double-strand breaks at replication forks, leading to rDNA copy number variation and DNA fragmentation. Torsional stress generated by R-loops also results in the accumulation of Top1. These abnormalities are partially dependent on canonical amplification recombination pathways, including those regulated by replication fork blocking and non-coding transcription.
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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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