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Subtelomere-binding protein Tbf1 and telomere-binding protein Rap1 collaborate to inhibit localization of the Mre11 complex to DNA ends in budding yeast.

Chromosome ends, known as telomeres, have to be distinguished from DNA double-strand breaks that activate DNA damage checkpoints. In budding yeast, the Mre11-Rad50-Xrs2 (MRX) complex associates with DNA ends and promotes checkpoint activation. Rap1 binds to double-stranded telomeric regions and recruits Rif1 and Rif2 to telomeres. Rap1 collaborates with Rif1 and Rif2 and inhibits MRX localization to DNA ends. This Rap1-Rif1-Rif2 function becomes attenuated at shortened telomeres. Here we show that Rap1 acts together with the subtelomere-binding protein Tbf1 and inhibits MRX localization to DNA ends. The placement of a subtelomeric sequence or TTAGGG repeats together with a short telomeric TG repeat sequence inhibits MRX accumulation at nearby DNA ends in a Tbf1-dependent manner. Moreover, tethering of both Tbf1 and Rap1 proteins decreases MRX and Tel1 accumulation at nearby DNA ends. This Tbf1- and Rap1-dependent pathway operates independently of Rif1 or Rif2 function. Depletion of Tbf1 protein stimulates checkpoint activation in cells containing short telomeres but not in cells containing normal-length telomeres. These data support a model in which Tbf1 and Rap1 collaborate to maintain genomic stability of short telomeres.

Pubmed ID: 22130795


  • Fukunaga K
  • Hirano Y
  • Sugimoto K


Molecular biology of the cell

Publication Data

January 16, 2012

Associated Grants

  • Agency: NCI NIH HHS, Id: CA148939
  • Agency: NIGMS NIH HHS, Id: GM073876
  • Agency: NCI NIH HHS, Id: R01 CA148939
  • Agency: NIGMS NIH HHS, Id: R01 GM073876

Mesh Terms

  • Amino Acid Sequence
  • DNA, Fungal
  • DNA-Binding Proteins
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • Molecular Sequence Data
  • Repressor Proteins
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Telomere
  • Telomere-Binding Proteins
  • Transcription Factors