Homologous recombination restarts blocked replication forks at the expense of genome rearrangements by template exchange

Mol Cell. 2010 Aug 13;39(3):346-59. doi: 10.1016/j.molcel.2010.07.015.


Template switching induced by stalled replication forks has recently been proposed to underlie complex genomic rearrangements. However, the resulting models are not supported by robust physical evidence. Here, we analyzed replication and recombination intermediates in a well-defined fission yeast system that blocks replication forks. We show that, in response to fork arrest, chromosomal rearrangements result from Rad52-dependent nascent strand template exchange occurring during fork restart. This template exchange occurs by both Rad51-dependent and -independent mechanisms. We demonstrate that Rqh1, the BLM homolog, limits Rad51-dependent template exchange without affecting fork restart. In contrast, we report that the Srs2 helicase promotes both fork restart and template exchange. Our data demonstrate that template exchange occurs during recombination-dependent fork restart at the expense of genome rearrangements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Replication / physiology*
  • DNA, Fungal / biosynthesis*
  • DNA, Fungal / genetics
  • Genome, Fungal / physiology*
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • Rad52 DNA Repair and Recombination Protein / genetics
  • Rad52 DNA Repair and Recombination Protein / metabolism
  • Recombination, Genetic / physiology*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism


  • DNA, Fungal
  • RHP51 protein, S pombe
  • Rad52 DNA Repair and Recombination Protein
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • SRS2 protein, S cerevisiae
  • Rad51 Recombinase
  • DNA Helicases
  • Rqh1 protein, S pombe