Reference - Detail
| RRC ID | 36020 |
|---|---|
| Author | Gadaleta MC, Das MM, Tanizawa H, Chang YT, Noma K, Nakamura TM, Noguchi E. |
| Title | Swi1Timeless Prevents Repeat Instability at Fission Yeast Telomeres. |
| Journal | PLoS Genet |
| Abstract |
Genomic instability associated with DNA replication stress is linked to cancer and genetic pathologies in humans. If not properly regulated, replication stress, such as fork stalling and collapse, can be induced at natural replication impediments present throughout the genome. The fork protection complex (FPC) is thought to play a critical role in stabilizing stalled replication forks at several known replication barriers including eukaryotic rDNA genes and the fission yeast mating-type locus. However, little is known about the role of the FPC at other natural impediments including telomeres. Telomeres are considered to be difficult to replicate due to the presence of repetitive GT-rich sequences and telomere-binding proteins. However, the regulatory mechanism that ensures telomere replication is not fully understood. Here, we report the role of the fission yeast Swi1(Timeless), a subunit of the FPC, in telomere replication. Loss of Swi1 causes telomere shortening in a telomerase-independent manner. Our epistasis analyses suggest that heterochromatin and telomere-binding proteins are not major impediments for telomere replication in the absence of Swi1. Instead, repetitive DNA sequences impair telomere integrity in swi1Δ mutant cells, leading to the loss of repeat DNA. In the absence of Swi1, telomere shortening is accompanied with an increased recruitment of Rad52 recombinase and more frequent amplification of telomere/subtelomeres, reminiscent of tumor cells that utilize the alternative lengthening of telomeres pathway (ALT) to maintain telomeres. These results suggest that Swi1 ensures telomere replication by suppressing recombination and repeat instability at telomeres. Our studies may also be relevant in understanding the potential role of Swi1(Timeless) in regulation of telomere stability in cancer cells. |
| Volume | 12(3) |
| Pages | e1005943 |
| Published | 2016-3-1 |
| DOI | 10.1371/journal.pgen.1005943 |
| PII | PGENETICS-D-15-02616 |
| PMID | 26990647 |
| PMC | PMC4798670 |
| MeSH | Cell Cycle Proteins / genetics* DNA Replication / genetics DNA-Binding Proteins / genetics* Genomic Instability Heterochromatin / genetics Humans Microsatellite Instability* Rad52 DNA Repair and Recombination Protein / genetics Repetitive Sequences, Nucleic Acid / genetics* Schizosaccharomyces / genetics Schizosaccharomyces pombe Proteins / genetics* Telomere / genetics Telomere Homeostasis Telomere Shortening / genetics Telomere-Binding Proteins / genetics* |
| IF | 5.175 |
| Times Cited | 12 |
| WOS Category | GENETICS & HEREDITY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 6 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Yeast | FY13724 FY14265 FY18508 FY14160 |