Regulation of Hed1 and Rad54 binding during maturation of the meiosis-specific presynaptic complex

EMBO J. 2018 Apr 3;37(7):e98728. doi: 10.15252/embj.201798728. Epub 2018 Feb 14.

Abstract

Most eukaryotes have two Rad51/RecA family recombinases, Rad51, which promotes recombination during mitotic double-strand break (DSB) repair, and the meiosis-specific recombinase Dmc1. During meiosis, the strand exchange activity of Rad51 is downregulated through interactions with the meiosis-specific protein Hed1, which helps ensure that strand exchange is driven by Dmc1 instead of Rad51. Hed1 acts by preventing Rad51 from interacting with Rad54, a cofactor required for promoting strand exchange during homologous recombination. However, we have a poor quantitative understanding of the regulatory interplay between these proteins. Here, we use real-time single-molecule imaging to probe how the Hed1- and Rad54-mediated regulatory network contributes to the identity of mitotic and meiotic presynaptic complexes. Based on our findings, we define a model in which kinetic competition between Hed1 and Rad54 helps define the functional identity of the presynaptic complex as cells undergo the transition from mitotic to meiotic repair.

Keywords: Rad51 recombinase; homologous recombination; meiosis; single‐molecule imaging.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • DNA Breaks, Double-Stranded
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Repair
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Homologous Recombination
  • Meiosis* / genetics
  • Mitosis
  • Rad51 Recombinase / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / isolation & purification
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Single Molecule Imaging

Substances

  • Cell Cycle Proteins
  • DMC1 protein, S cerevisiae
  • DNA-Binding Proteins
  • Hed1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • RAD51 protein, S cerevisiae
  • Rad51 Recombinase
  • RAD54 protein, S cerevisiae
  • DNA Helicases
  • DNA Repair Enzymes