Frequent Interchromosomal Template Switches during Gene Conversion in S. cerevisiae

Mol Cell. 2014 Aug 21;55(4):615-25. doi: 10.1016/j.molcel.2014.06.025. Epub 2014 Jul 24.


Although repair of double-strand breaks (DSBs) by gene conversion is the most accurate way to repair such lesions, in budding yeast there is a 1,000-fold increase in accompanying mutations, including interchromosomal template switches (ICTS) involving highly mismatched (homeologous) ectopic sequences. Although such events are rare and appear at a rate of 2 × 10(-7) when template jumps occur between 71% identical sequences, they are surprisingly frequent (0.3% of all repair events) when the second template is identical to the first, revealing the remarkable instability of repair DNA synthesis. With homeologous donors, ICTS uses microhomologies as small as 2 bp. Cells lacking mismatch repair proteins Msh6 and Mlh1 form chimeric recombinants with two distinct patches of microhomology, implying that these proteins are crucial for strand discrimination of heteroduplex DNA formed during ICTS. We identify the chromatin remodeler Rdh54 as the first protein required for template switching that does not affect simple gene conversion.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Base Sequence
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly / genetics*
  • Chromatin Assembly and Disassembly / physiology
  • Chromosomes, Fungal*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Mismatch Repair / genetics
  • DNA Mismatch Repair / physiology
  • DNA Topoisomerases / genetics
  • DNA Topoisomerases / metabolism
  • DNA, Fungal / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Conversion / genetics
  • Gene Conversion / physiology*
  • Genes, Fungal / genetics
  • Genes, Fungal / physiology
  • Genome, Fungal
  • Molecular Sequence Data
  • MutL Protein Homolog 1
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Homology, Nucleic Acid


  • Adaptor Proteins, Signal Transducing
  • Chromatin
  • DNA, Fungal
  • DNA-Binding Proteins
  • MLH1 protein, S cerevisiae
  • MSH6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • MutL Protein Homolog 1
  • DNA Helicases
  • DNA Topoisomerases
  • RDH54 protein, S cerevisiae