A global view of meiotic double-strand break end resection

Science. 2017 Jan 6;355(6320):40-45. doi: 10.1126/science.aak9704.

Abstract

DNA double-strand breaks that initiate meiotic recombination are exonucleolytically processed. This 5'→3' resection is a central, conserved feature of recombination but remains poorly understood. To address this lack, we mapped resection endpoints genome-wide at high resolution in Saccharomyces cerevisiae Full-length resection requires Exo1 exonuclease and the DSB-responsive kinase Tel1, but not Sgs1 helicase. Tel1 also promotes efficient and timely resection initiation. Resection endpoints display pronounced heterogeneity between genomic loci that reflects a tendency for nucleosomes to block Exo1, yet Exo1 also appears to digest chromatin with high processivity and at rates similar to naked DNA in vitro. This paradox points to nucleosome destabilization or eviction as a defining feature of the meiotic resection landscape.

Publication types

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

MeSH terms

  • Chromatin / metabolism
  • DNA Breaks, Double-Stranded*
  • Exodeoxyribonucleases / genetics
  • Exodeoxyribonucleases / metabolism
  • Genetic Loci
  • Homologous Recombination*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Meiosis*
  • Nucleosomes / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Chromatin
  • Intracellular Signaling Peptides and Proteins
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Protein Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae
  • Exodeoxyribonucleases
  • exodeoxyribonuclease I
  • SGS1 protein, S cerevisiae
  • RecQ Helicases