Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on short chromosomes

Nat Commun. 2019 Feb 27;10(1):970. doi: 10.1038/s41467-019-08875-x.


Faithful meiotic chromosome inheritance and fertility rely on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs, likely in response to initiation of crossover repair. In Saccharomyces cerevisiae, this regulation requires the removal of the conserved DSB-promoting protein Hop1/HORMAD during chromosome synapsis. Here, we identify privileged end-adjacent regions (EARs) spanning roughly 100 kb near all telomeres that escape DSB down-regulation. These regions retain Hop1 and continue to break in pachynema despite normal synaptonemal complex deposition. Differential retention of Hop1 requires the disassemblase Pch2/TRIP13, which preferentially removes Hop1 from telomere-distant sequences, and is modulated by the histone deacetylase Sir2 and the nucleoporin Nup2. Importantly, the uniform size of EARs among chromosomes contributes to disproportionately high DSB and repair signals on short chromosomes in pachynema, suggesting that EARs partially underlie the curiously high recombination rate of short chromosomes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Pairing / genetics
  • Chromosomes, Fungal / genetics*
  • Chromosomes, Fungal / metabolism
  • DNA Breaks, Double-Stranded*
  • DNA-Binding Proteins / metabolism
  • Meiosis / genetics*
  • Nuclear Pore Complex Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Recombination, Genetic
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
  • Sirtuin 2 / metabolism
  • Telomere / genetics*
  • Telomere / metabolism


  • DNA-Binding Proteins
  • HOP1 protein, S cerevisiae
  • NUP2 protein, S cerevisiae
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Pch2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Zip1 protein, S cerevisiae
  • SIR2 protein, S cerevisiae
  • Sirtuin 2