Late S phase-specific recruitment of Mre11 complex triggers hierarchical assembly of telomere replication proteins in Saccharomyces cerevisiae

Mol Cell. 2005 Feb 18;17(4):573-83. doi: 10.1016/j.molcel.2005.01.014.

Abstract

In Saccharomyces cerevisiae, telomere replication occurs in late S phase and is accompanied by dynamic remodeling of its protein components. Here, we show that MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in DNA double-strand break (DSB) repair, is recruited to the telomeres in late S phase. MRX is required for the late S phase-specific recruitment of ATR-like kinase Mec1 to the telomeres. Mec1, in turn, contributes to the assembly of the telomerase regulators Cdc13 and Est1 at the telomere ends. Our results provide a model for the hierarchical assembly of telomere-replication proteins in late S phase; this involves triggering by the loading of MRX onto the chromosome termini. The recruitment of DNA repair-related proteins to the telomeres at particular times in the cell cycle suggests that the normal terminus of a chromosome is recognized as a DSB during the course of replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin Immunoprecipitation
  • DNA / genetics
  • DNA Repair*
  • DNA Replication*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endodeoxyribonucleases / genetics*
  • Endodeoxyribonucleases / metabolism
  • Exodeoxyribonucleases / genetics*
  • Exodeoxyribonucleases / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Phenotype
  • Protein Serine-Threonine Kinases
  • S Phase*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Telomere / genetics*
  • Telomere / metabolism

Substances

  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • RAD50 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • XRS2 protein, S cerevisiae
  • DNA
  • MEC1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae