Reduced Rif2 and lack of Mec1 target short telomeres for elongation rather than double-strand break repair

Nat Struct Mol Biol. 2010 Dec;17(12):1438-45. doi: 10.1038/nsmb.1947. Epub 2010 Nov 7.

Abstract

Telomerase in Saccharomyces cerevisiae binds and preferentially elongates short telomeres, and this process requires the checkpoint kinase Tel1. Here we show that the Mre11 complex bound preferentially to short telomeres, which could explain the preferential binding of Tel1 to these ends. Compared to wild-type length telomeres, short telomeres generated by incomplete replication had low levels of the telomerase inhibitory protein Rif2. Moreover, in the absence of Rif2, Tel1 bound equally well to short and wild-type length telomeres, suggesting that low Rif2 content marks short telomeres for preferential elongation. In congenic strains, a double-strand break bound at least 140 times as much Mec1 in the first cell cycle after breakage as did a short telomere in the same time frame. Binding of replication protein A was also much lower at short telomeres. The absence of Mec1 at short telomeres could explain why they do not trigger a checkpoint-mediated cell-cycle arrest.

MeSH terms

  • Binding, Competitive
  • DNA Breaks, Double-Stranded*
  • DNA Repair*
  • DNA Replication
  • Endodeoxyribonucleases / metabolism
  • Exodeoxyribonucleases / metabolism
  • Histones / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Mutation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*
  • Replication Protein A / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Telomere / metabolism*
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism
  • Telomere-Binding Proteins / physiology*

Substances

  • Histones
  • Intracellular Signaling Peptides and Proteins
  • RFA1 protein, S cerevisiae
  • RIF2 protein, S cerevisiae
  • Replication Protein A
  • Saccharomyces cerevisiae Proteins
  • Telomere-Binding Proteins
  • gammaH2AX protein, S cerevisiae
  • MEC1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae