Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion

Elife. 2017 Jan 4;6:e21900. doi: 10.7554/eLife.21900.

Abstract

Gene conversions resulting from meiotic recombination are critical in shaping genome diversification and evolution. How the extent of gene conversions is regulated is unknown. Here we show that the budding yeast mismatch repair related MutLβ complex, Mlh1-Mlh2, specifically interacts with the conserved meiotic Mer3 helicase, which recruits it to recombination hotspots, independently of mismatch recognition. This recruitment is essential to limit gene conversion tract lengths genome-wide, without affecting crossover formation. Contrary to expectations, Mer3 helicase activity, proposed to extend the displacement loop (D-loop) recombination intermediate, does not influence the length of gene conversion events, revealing non-catalytical roles of Mer3. In addition, both purified Mer3 and MutLβ preferentially recognize D-loops, providing a mechanism for limiting gene conversion in vivo. These findings show that MutLβ is an integral part of a new regulatory step of meiotic recombination, which has implications to prevent rapid allele fixation and hotspot erosion in populations.

Keywords: S. cerevisiae; biochemistry; chromosomes; genes; meiosis; mismatch repair; recombination.

MeSH terms

  • Chromosomes, Fungal / metabolism
  • DNA Helicases / metabolism*
  • Gene Conversion*
  • MutL Protein Homolog 1 / metabolism*
  • MutL Proteins / metabolism*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • MLH1 protein, S cerevisiae
  • MLH2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • HFM1 protein, S cerevisiae
  • MutL Protein Homolog 1
  • MutL Proteins
  • DNA Helicases

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.