title: Crossover localisation is regulated by the neddylation posttranslational regulatory pathway.
abstract: Crossovers (COs) are at the origin of genetic variability, occurring across successive generations, and they are also essential for the correct segregation of chromosomes during meiosis. Their number and position are precisely controlled, however the mechanisms underlying these controls are poorly understood. Neddylation/rubylation is a regulatory pathway of posttranslational protein modification that is required for numerous cellular processes in eukaryotes, but has not yet been linked to homologous recombination. In a screen for meiotic recombination-defective mutants, we identified several axr1 alleles, disrupting the gene encoding the E1 enzyme of the neddylation complex in Arabidopsis. Using genetic and cytological approaches we found that axr1 mutants are characterised by a shortage in bivalent formation correlated with strong synapsis defects. We determined that the bivalent shortage in axr1 is not due to a general decrease in CO formation but rather due to a mislocalisation of class I COs. In axr1, as in wild type, COs are still under the control of the ZMM group of proteins. However, in contrast to wild type, they tend to cluster together and no longer follow the obligatory CO rule. Lastly, we showed that this deregulation of CO localisation is likely to be mediated by the activity of a cullin 4 RING ligase, known to be involved in DNA damage sensing during somatic DNA repair and mouse spermatogenesis. In conclusion, we provide evidence that the neddylation/rubylation pathway of protein modification is a key regulator of meiotic recombination. We propose that rather than regulating the number of recombination events, this pathway regulates their localisation, through the activation of cullin 4 RING ligase complexes. Possible targets for these ligases are discussed.
authors.affiliation: INRA, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France; AgroParisTech, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France.
authors.forename: Marina Tagliaro
authors.initials: MT
authors.lastname: Jahns
authors.affiliation: INRA, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France; AgroParisTech, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vezon
authors.affiliation: INRA, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France; AgroParisTech, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chambon
authors.affiliation: INRA, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France; AgroParisTech, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Pereira
authors.affiliation: Institut National de la Recherche Agronomique, Unité Mixte de Recherche de Génétique Végétale, Université Paris-Sud, Gif-sur-Yvette, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Falque
authors.affiliation: Institut National de la Recherche Agronomique, Unité Mixte de Recherche de Génétique Végétale, Université Paris-Sud, Gif-sur-Yvette, France.
authors.forename: Olivier C
authors.initials: OC
authors.lastname: Martin
authors.affiliation: INRA, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France; AgroParisTech, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France.
authors.forename: Liudmila
authors.initials: L
authors.lastname: Chelysheva
authors.affiliation: INRA, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France; AgroParisTech, Institut Jean-Pierre Bourgin, UMR 1318, ERL CNRS 3559, Saclay Plant Sciences, RD10, Versailles, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Grelon
mesh_terms: D000818:Animals; D017360:Arabidopsis / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D023902:Chromosome Pairing; D032461:Chromosomes, Plant / Q000378:metabolism; D003434:Crossing Over, Genetic; D004843:Epistasis, Genetic; D008540:Meiosis / Q000235:genetics; D008677:Metaphase; D051379:Mice; D009154:Mutation / Q000235:genetics; D011499:Protein Processing, Post-Translational
chemical_list: C081977:AXR1 protein, Arabidopsis; D029681:Arabidopsis Proteins