High-resolution mapping of heteroduplex DNA formed during UV-induced and spontaneous mitotic recombination events in yeast

Elife. 2017 Jul 17;6:e28069. doi: 10.7554/eLife.28069.

Abstract

In yeast, DNA breaks are usually repaired by homologous recombination (HR). An early step for HR pathways is formation of a heteroduplex, in which a single-strand from the broken DNA molecule pairs with a strand derived from an intact DNA molecule. If the two strands of DNA are not identical, there will be mismatches within the heteroduplex DNA (hetDNA). In wild-type strains, these mismatches are repaired by the mismatch repair (MMR) system, producing a gene conversion event. In strains lacking MMR, the mismatches persist. Most previous studies involving hetDNA formed during mitotic recombination were restricted to one locus. Below, we present a global mapping of hetDNA formed in the MMR-defective mlh1 strain. We find that many recombination events are associated with repair of double-stranded DNA gaps and/or involve Mlh1-independent mismatch repair. Many of our events are not explicable by the simplest form of the double-strand break repair model of recombination.

Keywords: S. cerevisiae; chromosomes; gene conversion; genes; genome rearrangements; genome-wide mapping; heteroduplex DNA; mismatch repair; mitotic recombination.

MeSH terms

  • Brain Neoplasms
  • Colorectal Neoplasms
  • DNA, Fungal / genetics*
  • Mitosis / radiation effects*
  • MutL Protein Homolog 1 / deficiency
  • Neoplastic Syndromes, Hereditary
  • Nucleic Acid Heteroduplexes / analysis*
  • Recombination, Genetic*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae / radiation effects*
  • Saccharomyces cerevisiae Proteins
  • Ultraviolet Rays*

Substances

  • DNA, Fungal
  • MLH1 protein, S cerevisiae
  • Nucleic Acid Heteroduplexes
  • Saccharomyces cerevisiae Proteins
  • MutL Protein Homolog 1

Supplementary concepts

  • Turcot syndrome