Rad59-facilitated acquisition of Y' elements by short telomeres delays the onset of senescence

PLoS Genet. 2014 Nov 6;10(11):e1004736. doi: 10.1371/journal.pgen.1004736. eCollection 2014 Nov.

Abstract

Telomerase-negative yeasts survive via one of the two Rad52-dependent recombination pathways, which have distinct genetic requirements. Although the telomere pattern of type I and type II survivors is well characterized, the mechanistic details of short telomere rearrangement into highly evolved pattern observed in survivors are still missing. Here, we analyze immediate events taking place at the abruptly shortened VII-L and native telomeres. We show that short telomeres engage in pairing with internal Rap1-bound TG1-3-like tracts present between subtelomeric X and Y' elements, which is followed by BIR-mediated non-reciprocal translocation of Y' element and terminal TG1-3 repeats from the donor end onto the shortened telomere. We found that choice of the Y' donor was not random, since both engineered telomere VII-L and native VI-R acquired Y' elements from partially overlapping sets of specific chromosome ends. Although short telomere repair was associated with transient delay in cell divisions, Y' translocation on native telomeres did not require Mec1-dependent checkpoint. Furthermore, the homeologous pairing between the terminal TG1-3 repeats at VII-L and internal repeats on other chromosome ends was largely independent of Rad51, but instead it was facilitated by Rad59 that stimulates Rad52 strand annealing activity. Therefore, Y' translocation events taking place during presenescence are genetically separable from Rad51-dependent Y' amplification process that occurs later during type I survivor formation. We show that Rad59-facilitated Y' translocations on X-only telomeres delay the onset of senescence while preparing ground for type I survivor formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • Rad52 DNA Repair and Recombination Protein / genetics*
  • Rad52 DNA Repair and Recombination Protein / metabolism
  • Recombination, Genetic*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Telomerase / genetics
  • Telomere / genetics*
  • Telomere Shortening / genetics

Substances

  • DNA-Binding Proteins
  • RAD52 protein, S cerevisiae
  • RAD59 protein, S cerevisiae
  • Rad52 DNA Repair and Recombination Protein
  • Saccharomyces cerevisiae Proteins
  • Rad51 Recombinase
  • Telomerase

Grants and funding

This work was supported by the “Ligue Nationale Contre le Cancer” and by “L'Institut National Du Cancer (INCA), programme TELOCHROM”. DC was supported by the “Association pour la Recherche sur le Cancer” (ARC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.