title: Multiple mechanisms limit meiotic crossovers: TOP3α and two BLM homologs antagonize crossovers in parallel to FANCM.
abstract: Meiotic crossovers (COs) have two important roles, shuffling genetic information and ensuring proper chromosome segregation. Despite their importance and a large excess of precursors (i.e., DNA double-strand breaks, DSBs), the number of COs is tightly regulated, typically one to three per chromosome pair. The mechanisms ensuring that most DSBs are repaired as non-COs and the evolutionary forces imposing this constraint are poorly understood. Here we identified Topoisomerase3α (TOP3α) and the RECQ4 helicases--the Arabidopsis slow growth suppressor 1 (Sgs1)/Bloom syndrome protein (BLM) homologs--as major barriers to meiotic CO formation. First, the characterization of a specific TOP3α mutant allele revealed that, in addition to its role in DNA repair, this topoisomerase antagonizes CO formation. Further, we found that RECQ4A and RECQ4B constitute the strongest meiotic anti-CO activity identified to date, their concomitant depletion leading to a sixfold increase in CO frequency. In both top3α and recq4ab mutants, DSB number is unaffected, and extra COs arise from a normally minor pathway. Finally, both TOP3α and RECQ4A/B act independently of the previously identified anti-CO Fanconi anemia of complementation group M (FANCM) helicase. This finding shows that several parallel pathways actively limit CO formation and suggests that the RECQA/B and FANCM helicases prevent COs by processing different substrates. Despite a ninefold increase in CO frequency, chromosome segregation was unaffected. This finding supports the idea that CO number is restricted not because of mechanical constraints but likely because of the long-term costs of recombination. Furthermore, this work demonstrates how manipulating a few genes holds great promise for increasing recombination frequency in plant-breeding programs.
authors.affiliation: Institut Jean-Pierre Bourgin, UMR1318, équipes de recherche labellisées CNRS 3559, National Institute for Agricultural Research, Saclay Plant Sciences, 78000 Versailles, France; Institut Jean-Pierre Bourgin, UMR 1318, équipes de recherche labellisées CNRS 3559, AgroParisTech, Saclay Plant Sciences, 78000 Versailles, France;
authors.forename: Mathilde
authors.initials: M
authors.lastname: Séguéla-Arnaud
authors.affiliation: Institut Jean-Pierre Bourgin, UMR1318, équipes de recherche labellisées CNRS 3559, National Institute for Agricultural Research, Saclay Plant Sciences, 78000 Versailles, France; Institut Jean-Pierre Bourgin, UMR 1318, équipes de recherche labellisées CNRS 3559, AgroParisTech, Saclay Plant Sciences, 78000 Versailles, France;
authors.forename: Wayne
authors.initials: W
authors.lastname: Crismani
authors.affiliation: Institut Jean-Pierre Bourgin, UMR1318, équipes de recherche labellisées CNRS 3559, National Institute for Agricultural Research, Saclay Plant Sciences, 78000 Versailles, France; Institut Jean-Pierre Bourgin, UMR 1318, équipes de recherche labellisées CNRS 3559, AgroParisTech, Saclay Plant Sciences, 78000 Versailles, France;
authors.forename: Cécile
authors.initials: C
authors.lastname: Larchevêque
authors.affiliation: Institut Jean-Pierre Bourgin, UMR1318, équipes de recherche labellisées CNRS 3559, National Institute for Agricultural Research, Saclay Plant Sciences, 78000 Versailles, France; Institut Jean-Pierre Bourgin, UMR 1318, équipes de recherche labellisées CNRS 3559, AgroParisTech, Saclay Plant Sciences, 78000 Versailles, France;
authors.forename: Julien
authors.initials: J
authors.lastname: Mazel
authors.affiliation: Institut Jean-Pierre Bourgin, UMR1318, équipes de recherche labellisées CNRS 3559, National Institute for Agricultural Research, Saclay Plant Sciences, 78000 Versailles, France; Institut Jean-Pierre Bourgin, UMR 1318, équipes de recherche labellisées CNRS 3559, AgroParisTech, Saclay Plant Sciences, 78000 Versailles, France;
authors.forename: Nicole
authors.initials: N
authors.lastname: Froger
authors.affiliation: Institut Jean-Pierre Bourgin, UMR1318, équipes de recherche labellisées CNRS 3559, National Institute for Agricultural Research, Saclay Plant Sciences, 78000 Versailles, France; Institut Jean-Pierre Bourgin, UMR 1318, équipes de recherche labellisées CNRS 3559, AgroParisTech, Saclay Plant Sciences, 78000 Versailles, France;
authors.forename: Sandrine
authors.initials: S
authors.lastname: Choinard
authors.affiliation: Institut Jean-Pierre Bourgin, UMR1318, équipes de recherche labellisées CNRS 3559, National Institute for Agricultural Research, Saclay Plant Sciences, 78000 Versailles, France; Institut Jean-Pierre Bourgin, UMR 1318, équipes de recherche labellisées CNRS 3559, AgroParisTech, Saclay Plant Sciences, 78000 Versailles, France;
authors.forename: Afef
authors.initials: A
authors.lastname: Lemhemdi
authors.affiliation: Institut Jean-Pierre Bourgin, UMR1318, équipes de recherche labellisées CNRS 3559, National Institute for Agricultural Research, Saclay Plant Sciences, 78000 Versailles, France; Institut Jean-Pierre Bourgin, UMR 1318, équipes de recherche labellisées CNRS 3559, AgroParisTech, Saclay Plant Sciences, 78000 Versailles, France;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Macaisne
authors.affiliation: Department of Plant Systems Biology, Flanders Institute for Biotechnology, B-9052 Ghent, Belgium; Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Ghent, Belgium;
authors.forename: Jelle
authors.initials: J
authors.lastname: Van Leene
authors.affiliation: Department of Medical Protein Research, Flanders Institute for Biotechnology, B-9000 Ghent, Belgium; and Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Gevaert
authors.affiliation: Department of Plant Systems Biology, Flanders Institute for Biotechnology, B-9052 Ghent, Belgium; Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Ghent, Belgium;
authors.forename: Geert
authors.initials: G
authors.lastname: De Jaeger
authors.affiliation: Institut Jean-Pierre Bourgin, UMR1318, équipes de recherche labellisées CNRS 3559, National Institute for Agricultural Research, Saclay Plant Sciences, 78000 Versailles, France; Institut Jean-Pierre Bourgin, UMR 1318, équipes de recherche labellisées CNRS 3559, AgroParisTech, Saclay Plant Sciences, 78000 Versailles, France;
authors.forename: Liudmilla
authors.initials: L
authors.lastname: Chelysheva
authors.affiliation: Institut Jean-Pierre Bourgin, UMR1318, équipes de recherche labellisées CNRS 3559, National Institute for Agricultural Research, Saclay Plant Sciences, 78000 Versailles, France; Institut Jean-Pierre Bourgin, UMR 1318, équipes de recherche labellisées CNRS 3559, AgroParisTech, Saclay Plant Sciences, 78000 Versailles, France; raphael.mercier@versailles.inra.fr.
authors.forename: Raphael
authors.initials: R
authors.lastname: Mercier
mesh_terms: D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D003434:Crossing Over, Genetic; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000235:genetics* / Q000378:metabolism; D008540:Meiosis / Q000235:genetics*; D009154:Mutation; D010802:Phylogeny; D030821:Plants, Genetically Modified; D011995:Recombination, Genetic
chemical_list: D029681:Arabidopsis Proteins; D004265:DNA Helicases; C573664:FANCM protein, Arabidopsis; C514439:RecQ4A protein, Arabidopsis; D004264:DNA Topoisomerases, Type I
keywords: RECQ4; Topoisomerase 3; crossover; meiosis; recombination
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