Differential association of the conserved SUMO ligase Zip3 with meiotic double-strand break sites reveals regional variations in the outcome of meiotic recombination

PLoS Genet. 2013 Apr;9(4):e1003416. doi: 10.1371/journal.pgen.1003416. Epub 2013 Apr 4.

Abstract

During the first meiotic prophase, programmed DNA double-strand breaks (DSBs) are distributed non randomly at hotspots along chromosomes, to initiate recombination. In all organisms, more DSBs are formed than crossovers (CO), the repair product that creates a physical link between homologs and allows their correct segregation. It is not known whether all DSB hotspots are also CO hotspots or if the CO/DSB ratio varies with the chromosomal location. Here, we investigated the variations in the CO/DSB ratio by mapping genome-wide the binding sites of the Zip3 protein during budding yeast meiosis. We show that Zip3 associates with DSB sites that are engaged in repair by CO, and Zip3 enrichment at DSBs reflects the DSB tendency to be repaired by CO. Moreover, the relative amount of Zip3 per DSB varies with the chromosomal location, and specific chromosomal features are associated with high or low Zip3 per DSB. This work shows that DSB hotspots are not necessarily CO hotspots and suggests that different categories of DSB sites may fulfill different functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Fungal / genetics
  • Crossing Over, Genetic*
  • DNA Breaks, Double-Stranded
  • DNA Repair / genetics
  • Homologous Recombination*
  • Meiosis / genetics*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Ubiquitin-Protein Ligases* / genetics
  • Ubiquitin-Protein Ligases* / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Ubiquitin-Protein Ligases
  • Zip3 protein, S cerevisiae

Grants and funding

Work in the authors' laboratory is supported by an Atip grant from the CNRS, by the Association pour la Recherche sur le Cancer (http://www.recherche-cancer.net/), La Ligue contre le Cancer (http://www.ligue-cancer.net/pages/chercheurs), La Fondation pour la Recherche Médicale (http://www.frm.org/l-aide-de-la-fondation-aux-chercheurs.html), and ANR Blanc (MeiChrono). M-ES was supported by post-doctoral grants from CNRS, Institut Curie, and Fondation pour la Recherche Médicale. VS was supported by a PhD studentship from the Ministère de l'Enseignement Supérieur. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.