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Telomere-binding proteins Taz1 and Rap1 regulate DSB repair and suppress gross chromosomal rearrangements in fission yeast.
Irie, Hiroyuki; Yamamoto, Io; Tarumoto, Yusuke; Tashiro, Sanki; Runge, Kurt W; Ishikawa, Fuyuki.
Afiliación
  • Irie H; Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Yamamoto I; Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Tarumoto Y; Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Tashiro S; Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Runge KW; Department of Molecular Genetics, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, United States of America.
  • Ishikawa F; Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan.
PLoS Genet ; 15(8): e1008335, 2019 08.
Article en En | MEDLINE | ID: mdl-31454352
Genomic rearrangements (gross chromosomal rearrangements, GCRs) threatens genome integrity and cause cell death or tumor formation. At the terminus of linear chromosomes, a telomere-binding protein complex, called shelterin, ensures chromosome stability by preventing chromosome end-to-end fusions and regulating telomere length homeostasis. As such, shelterin-mediated telomere functions play a pivotal role in suppressing GCR formation. However, it remains unclear whether the shelterin proteins play any direct role in inhibiting GCR at non-telomeric regions. Here, we have established a GCR assay for the first time in fission yeast and measured GCR rates in various mutants. We found that fission yeast cells lacking shelterin components Taz1 or Rap1 (mammalian TRF1/2 or RAP1 homologues, respectively) showed higher GCR rates compared to wild-type, accumulating large chromosome deletions. Genetic dissection of Rap1 revealed that Rap1 contributes to inhibiting GCRs via two independent pathways. The N-terminal BRCT-domain promotes faithful DSB repair, as determined by I-SceI-mediated DSB-induction experiments; moreover, association with Poz1 mediated by the central Poz1-binding domain regulates telomerase accessibility to DSBs, leading to suppression of de novo telomere additions. Our data highlight unappreciated functions of the shelterin components Taz1 and Rap1 in maintaining genome stability, specifically by preventing non-telomeric GCRs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Schizosaccharomyces / Reordenamiento Génico / Proteínas de Schizosaccharomyces pombe / Proteínas de Unión a Telómeros / Reparación del ADN Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Schizosaccharomyces / Reordenamiento Génico / Proteínas de Schizosaccharomyces pombe / Proteínas de Unión a Telómeros / Reparación del ADN Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos