Mechanistic View and Genetic Control of DNA Recombination during Meiosis

Mol Cell. 2018 Apr 5;70(1):9-20.e6. doi: 10.1016/j.molcel.2018.02.032.

Abstract

Meiotic recombination is essential for fertility and allelic shuffling. Canonical recombination models fail to capture the observed complexity of meiotic recombinants. Here, by combining genome-wide meiotic heteroduplex DNA patterns with meiotic DNA double-strand break (DSB) sites, we show that part of this complexity results from frequent template switching during synthesis-dependent strand annealing that yields noncrossovers and from branch migration of double Holliday junction (dHJ)-containing intermediates that mainly yield crossovers. This complexity also results from asymmetric positioning of crossover intermediates relative to the initiating DSB and Msh2-independent conversions promoted by the suspected dHJ resolvase Mlh1-3 as well as Exo1 and Sgs1. Finally, we show that dHJ resolution is biased toward cleavage of the pair of strands containing newly synthesized DNA near the junctions and that this bias can be decoupled from the crossover-biased dHJ resolution. These properties are likely conserved in eukaryotes containing ZMM proteins, which includes mammals.

Keywords: Holliday junction; crossover; gene conversion; heteroduplex DNA; homologous recombination; meiosis; mismatch repair; noncrossover; resolvase; structure specific nuclease.

Publication types

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

MeSH terms

  • DNA Breaks, Double-Stranded*
  • DNA, Cruciform*
  • DNA, Fungal / genetics*
  • DNA, Fungal / metabolism
  • Exodeoxyribonucleases / genetics
  • Exodeoxyribonucleases / metabolism
  • Meiosis*
  • MutL Protein Homolog 1 / genetics
  • MutL Protein Homolog 1 / metabolism
  • MutL Proteins / genetics
  • MutL Proteins / metabolism
  • Nucleic Acid Conformation
  • Nucleic Acid Heteroduplexes / genetics*
  • Nucleic Acid Heteroduplexes / metabolism
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism
  • Recombination, Genetic*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • DNA, Cruciform
  • DNA, Fungal
  • MLH1 protein, S cerevisiae
  • MLH2 protein, S cerevisiae
  • MLH3 protein, S cerevisiae
  • Nucleic Acid Heteroduplexes
  • Saccharomyces cerevisiae Proteins
  • Exodeoxyribonucleases
  • exodeoxyribonuclease I
  • SGS1 protein, S cerevisiae
  • MutL Protein Homolog 1
  • MutL Proteins
  • RecQ Helicases