Homologue engagement controls meiotic DNA break number and distribution

Nature. 2014 Jun 12;510(7504):241-6. doi: 10.1038/nature13120. Epub 2014 Apr 6.

Abstract

Meiotic recombination promotes genetic diversification as well as pairing and segregation of homologous chromosomes, but the double-strand breaks (DSBs) that initiate recombination are dangerous lesions that can cause mutation or meiotic failure. How cells control DSBs to balance between beneficial and deleterious outcomes is not well understood. Here we test the hypothesis that DSB control involves a network of intersecting negative regulatory circuits. Using multiple complementary methods, we show that DSBs form in greater numbers in Saccharomyces cerevisiae cells lacking ZMM proteins, a suite of recombination-promoting factors traditionally regarded as acting strictly downstream of DSB formation. ZMM-dependent DSB control is genetically distinct from a pathway tying break formation to meiotic progression through the Ndt80 transcription factor. These counterintuitive findings suggest that homologous chromosomes that have successfully engaged one another stop making breaks. Genome-wide DSB maps uncover distinct responses by different subchromosomal domains to the ZMM mutation zip3 (also known as cst9), and show that Zip3 is required for the previously unexplained tendency of DSB density to vary with chromosome size. Thus, feedback tied to ZMM function contributes in unexpected ways to spatial patterning of recombination.

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*
  • Crossing Over, Genetic / genetics
  • DNA Breaks, Double-Stranded*
  • DNA-Binding Proteins / metabolism
  • Epistasis, Genetic
  • Genome, Fungal / genetics
  • Homologous Recombination / genetics*
  • Meiosis / genetics*
  • Mutation / genetics
  • Phenotype
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factors / metabolism
  • Ubiquitin-Protein Ligases / genetics

Substances

  • DNA-Binding Proteins
  • NDT80 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Ubiquitin-Protein Ligases
  • Zip3 protein, S cerevisiae

Associated data

  • GEO/GSE48299