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Swi1 Timeless Prevents Repeat Instability at Fission Yeast Telomeres
Author(s) -
Noguchi Eishi,
Gadaleta Mariana
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.560.8
Subject(s) - telomere , telomerase , genome instability , telomere binding protein , biology , dna replication , genetics , homologous recombination , heterochromatin , replication protein a , microbiology and biotechnology , dna , chromatin , dna damage , dna binding protein , gene , transcription factor
Genomic instability associated with DNA replication stress is linked to cancer and genetic pathologies in humans. Replication stress, such as fork stalling and collapse, can arise at natural impediments present throughout the genome if not properly regulated. These impediments include telomeres, which contain repetitive DNA sequences and abundant DNA‐binding proteins. Due to such natures, telomeres are considered to be difficult to replicate. However, the mechanism of telomere replication remains elusive. In this report, we describe a genome‐wide study that identifies the Swi1 Timeless protein as a critical factor to prevent repeat instability and recombination at telomeres. Loss of Swi1 causes telomere and subtelomere shortening in a telomerase‐independent manner. Our genetic studies 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 swi1 Δ mutant cells, leading to the loss of repeat DNAs. In the absence of Swi1, telomere shortening is accompanied with an increased recruitment of Rad52 recombinase, silencing defects, and activation of the alternative lengthening of telomeres pathway (ALT) in telomerase‐negative cells. These results suggest that Swi1 ensures telomere replication by suppressing recombination and repeat instability at telomeres. Our studies may also contribute to the understanding the mechanism of ALT in human cancers.