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Ccq1 restrains Mre11-mediated degradation to distinguish short telomeres from double-strand breaks.
Audry, Julien; Zhang, Haitao; Kerr, Carly; Berkner, Kathleen L; Runge, Kurt W.
Afiliação
  • Audry J; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
  • Zhang H; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
  • Kerr C; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
  • Berkner KL; Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
  • Runge KW; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Nucleic Acids Res ; 52(7): 3722-3739, 2024 Apr 24.
Article em En | MEDLINE | ID: mdl-38321948
ABSTRACT
Telomeres protect chromosome ends and are distinguished from DNA double-strand breaks (DSBs) by means of a specialized chromatin composed of DNA repeats bound by a multiprotein complex called shelterin. We investigated the role of telomere-associated proteins in establishing end-protection by studying viable mutants lacking these proteins. Mutants were studied using a Schizosaccharomyces pombe model system that induces cutting of a 'proto-telomere' bearing telomere repeats to rapidly form a new stable chromosomal end, in contrast to the rapid degradation of a control DSB. Cells lacking the telomere-associated proteins Taz1, Rap1, Poz1 or Rif1 formed a chromosome end that was stable. Surprisingly, cells lacking Ccq1, or impaired for recruiting Ccq1 to the telomere, converted the cleaved proto-telomere to a rapidly degraded DSB. Ccq1 recruits telomerase, establishes heterochromatin and affects DNA damage checkpoint activation; however, these functions were separable from protection of the new telomere by Ccq1. In cells lacking Ccq1, telomere degradation was greatly reduced by eliminating the nuclease activity of Mre11 (part of the Mre11-Rad50-Nbs1/Xrs2 DSB processing complex), and higher amounts of nuclease-deficient Mre11 associated with the new telomere. These results demonstrate a novel function for S. pombe Ccq1 to effect end-protection by restraining Mre11-dependent degradation of the DNA end.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Schizosaccharomyces / Telômero / Proteínas de Schizosaccharomyces pombe / Proteínas de Ligação a Telômeros / Quebras de DNA de Cadeia Dupla Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Schizosaccharomyces / Telômero / Proteínas de Schizosaccharomyces pombe / Proteínas de Ligação a Telômeros / Quebras de DNA de Cadeia Dupla Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2024 Tipo de documento: Article