The S-Phase Cyclin Clb5 Promotes rRNA Gene (rDNA) Stability by Maintaining Replication Initiation Efficiency in rDNA
| Autor: | Takehiko Kobayashi, Mariko Sasaki, Mayuko Goto |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Genome instability
DNA Replication Saccharomyces cerevisiae Proteins ribosomal RNA gene DNA polymerase Saccharomyces cerevisiae Cyclin B Origin of replication DNA Ribosomal Genomic Instability S Phase 03 medical and health sciences chemistry.chemical_compound replication fork arrest Gene duplication Clb5 DNA Fungal Molecular Biology Gene 030304 developmental biology 0303 health sciences replication origin biology fungi 030302 biochemistry & molecular biology Genes rRNA Cell Biology genome instability Cell biology Replication fork arrest DNA-Binding Proteins chemistry Replication Initiation biology.protein DNA DNA Damage Research Article |
| Zdroj: | Molecular and Cellular Biology |
| ISSN: | 1098-5549 |
| Popis: | Regulation of replication origins is important for complete duplication of the genome, but the effect of origin activation on the cellular response to replication stress is poorly understood. The budding yeast rRNA gene (rDNA) forms tandem repeats and undergoes replication fork arrest at the replication fork barrier (RFB), inducing DNA double-strand breaks (DSBs) and genome instability accompanied by copy number alterations. Regulation of replication origins is important for complete duplication of the genome, but the effect of origin activation on the cellular response to replication stress is poorly understood. The budding yeast rRNA gene (rDNA) forms tandem repeats and undergoes replication fork arrest at the replication fork barrier (RFB), inducing DNA double-strand breaks (DSBs) and genome instability accompanied by copy number alterations. Here, we demonstrate that the S-phase cyclin Clb5 promotes rDNA stability. Absence of Clb5 led to reduced efficiency of replication initiation in rDNA but had little effect on the number of replication forks arrested at the RFB, suggesting that arrival of the converging fork is delayed and forks are more stably arrested at the RFB. Deletion of CLB5 affected neither DSB formation nor its repair at the RFB but led to homologous recombination-dependent rDNA instability. Therefore, arrested forks at the RFB may be subject to DSB-independent, recombination-dependent rDNA instability. The rDNA instability in clb5Δ was not completely suppressed by the absence of Fob1, which is responsible for fork arrest at the RFB. Thus, Clb5 establishes the proper interval for active replication origins and shortens the travel distance for DNA polymerases, which may reduce Fob1-independent DNA damage. |
| Databáze: | OpenAIRE |
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