Rif1 and rif2 inhibit localization of tel1 to DNA ends

Mol Cell. 2009 Feb 13;33(3):312-22. doi: 10.1016/j.molcel.2008.12.027.

Abstract

Chromosome ends, known as telomeres, have to be distinguished from DNA double-strand breaks (DSBs) that activate the DNA-damage checkpoint. In budding yeast, the ATM homolog Tel1 associates preferentially with short telomeres and promotes telomere addition. Here, we show that the telomeric proteins Rif1 and Rif2 attenuate Tel1 recruitment to DNA ends through distinct mechanisms. Both Rif1 and Rif2 inhibit the localization of Tel1, but not the Mre11-Rad50-Xrs2 (MRX) complex, to adjacent DNA ends. Rif1 function is weaker at short telomeric repeats compared with Rif2 function and is partly dependent on Rif2. Rif2 competes with Tel1 for binding to the C terminus of Xrs2. Once Tel1 is delocalized, MRX does not associate efficiently with Rap1-covered DNA ends. These results reveal a mechanism by which telomeric DNA sequences mask DNA ends from Tel1 recognition for the regulation of telomere length.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carrier Proteins / metabolism*
  • DNA Breaks, Double-Stranded
  • DNA, Fungal / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism
  • Exodeoxyribonucleases / genetics
  • Exodeoxyribonucleases / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Telomere / metabolism
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Carrier Proteins
  • DNA, Fungal
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • RAD50 protein, S cerevisiae
  • RAP1 protein, S cerevisiae
  • RIF2 protein, S cerevisiae
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Telomere-Binding Proteins
  • Transcription Factors
  • XRS2 protein, S cerevisiae
  • RIF1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae