title: Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion.
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.
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3664, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Duroc
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3664, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
authors.forename: Lepakshi
authors.initials: L
authors.lastname: Ranjha
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3664, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Adam
authors.affiliation: I2BC, iBiTec-S, CEA, CNRS UMR 9198, Université Paris-Sud, Gif-sur-Yvette, France.|Université Paris Sud, Orsay, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Guérois
authors.affiliation: CRCM, Inserm U1068, Institut Paoli-Calmettes, Aix-Marseille Université UM105, CNRS UMR7258, Marseille, France.
authors.forename: Khan
authors.initials: K
authors.lastname: Md Muntaz
authors.affiliation: I2BC, iBiTec-S, CEA, CNRS UMR 9198, Université Paris-Sud, Gif-sur-Yvette, France.|Université Paris Sud, Orsay, France.|Musée de l'Homme, CNRS UMR 7206, Paris, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Marsolier-Kergoat
authors.affiliation: Institut Curie, Centre de Recherche, PSL Research University, LSMP, Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Dingli
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3664, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Laureau
authors.affiliation: Institut Curie, Centre de Recherche, PSL Research University, LSMP, Paris, France.
authors.forename: Damarys
authors.initials: D
authors.lastname: Loew
authors.affiliation: CRCM, Inserm U1068, Institut Paoli-Calmettes, Aix-Marseille Université UM105, CNRS UMR7258, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Llorente
authors.affiliation: I2BC, iBiTec-S, CEA, CNRS UMR 9198, Université Paris-Sud, Gif-sur-Yvette, France.|Université Paris Sud, Orsay, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Charbonnier
authors.affiliation: Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
authors.forename: Petr
authors.identifier: 0000-0002-9087-032X
authors.initials: P
authors.lastname: Cejka
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3664, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Valérie
authors.identifier: 0000-0001-6520-2461
authors.initials: V
authors.lastname: Borde
mesh_terms: D015825:Chromosomes, Fungal / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism*; D005785:Gene Conversion; D000070957:MutL Protein Homolog 1 / Q000378:metabolism*; D000070956:MutL Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C088859:MLH1 protein, S cerevisiae; C497822:MLH2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C455499:HFM1 protein, S cerevisiae; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D004265:DNA Helicases
keywords: S. cerevisiae; biochemistry; chromosomes; genes; meiosis; mismatch repair; recombination