The logic and mechanism of homologous recombination partner choice

Mol Cell. 2013 Aug 22;51(4):440-53. doi: 10.1016/j.molcel.2013.08.008.

Abstract

Recombinational repair of spontaneous double-strand breaks (DSBs) exhibits sister bias. DSB-initiated meiotic recombination exhibits homolog bias. Physical analysis in yeast reveals that, in both cases, the recombination reaction intrinsically gives homolog bias. From this baseline default, cohesin intervenes to confer sister bias, likely independent of cohesion. In meiosis, cohesin's sister-biasing effect is counteracted by RecA homolog Rad51 and its mediators, plus meiotic RecA homolog Dmc1, which thereby restore intrinsic homolog bias. Meiotic axis complex Red1/Mek1/Hop1 participates by cleanly switching recombination from mitotic to meiotic mode, concomitantly activating Dmc1. We propose that a Rad51/DNA filament at one DSB end captures the intact sister, creating an anchor pad. This filament extends across the DSB site on the intact partner, precluding intersister strand exchange, thus forcing use of the homolog. Cohesin and Dmc1 interactively modulate this extension, with program-appropriate effects. In accord with this model, Rad51-mediated recombination in vivo requires the presence of a sister.

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
  • Cells, Cultured
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA Breaks, Double-Stranded
  • DNA Repair / genetics*
  • DNA, Fungal / analysis
  • DNA, Fungal / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Homologous Recombination / genetics*
  • MAP Kinase Kinase 1 / genetics
  • MAP Kinase Kinase 1 / metabolism
  • Meiosis / genetics*
  • Mutation / genetics
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DMC1 protein, S cerevisiae
  • DNA, Fungal
  • DNA-Binding Proteins
  • HOP1 protein, S cerevisiae
  • RED1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • cohesins
  • MAP Kinase Kinase 1
  • RAD51 protein, S cerevisiae
  • Rad51 Recombinase