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- Concerted action of the MutLĪ² heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion
Concerted action of the MutLĪ² heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion
Authors
Yann Duroc, Rajeev Kumar, Lepakshi Ranjha, CƩline Adam, Raphaƫl GuƩrois, Khan Md Muntaz, Marie-Claude Marsolier-Kergoat, Florent Dingli, Raphaƫlle Laureau, Damarys Loew, Bertrand Llorente, Jean-Baptiste Charbonnier, Petr Cejka, ValƩrie Borde
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 MutLĪ² 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 MutLĪ² preferentially recognize D-loops, providing a mechanism for limiting gene conversion in vivo. These findings show that MutLĪ² 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.