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.
Highlights
Meiotic recombination is a key evolutionary process that promotes genome diversification in sexually reproducing organisms
We show that the MutLb complex is recruited to meiotic recombination sites by the Mer3 helicase, and shows the unique ability to limit the length of gene conversions genomewide
This has important implications for the control of genome diversity created by gene conversion in meiosis
Summary
Meiotic recombination is a key evolutionary process that promotes genome diversification in sexually reproducing organisms. Recombination shuffles parental genomes through genetic exchanges leading to crossovers (COs) or noncrossovers (NCOs). Repair of Spo11-induced DNA double-strand breaks (DSBs) by recombination into COs is crucial for the formation of gametes with normal chromosome content. COs ensure a physical link between homologs that allows them to properly segregate to opposite poles during meiosis I division (Hunter, 2015). DSBs occur in excess over COs, so many DSBs repaired as noncrossovers (NCOs), without exchange of flanking sequences. Both COs and NCOs involve the formation of heteroduplex DNA, which can yield gene conversions after mismatch repair (Figure 1). Gene conversions consist of the unidirectional transfer of
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