RRC ID 36020
著者 Gadaleta MC, Das MM, Tanizawa H, Chang YT, Noma K, Nakamura TM, Noguchi E.
タイトル Swi1Timeless Prevents Repeat Instability at Fission Yeast Telomeres.
ジャーナル 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.
巻・号 12(3)
ページ e1005943
公開日 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
引用数 12
WOS 分野 GENETICS & HEREDITY
リソース情報
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