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.
During meiosis, two successive chromosomal divisions follow a single S phase, resulting in the formation of four haploid cells, each with half of the parental genetic material. This reduction in chromosome number occurs during the first meiotic division, when homologous chromosomes (paternal and maternal) are separated from each other. For this to happen, homologous chromosomes associate in structures called bivalents, where each chromosome is linked to its homologue by a point of contact known as chiasmata. These chiasmata reflect the formation of crossovers (COs), one of the manifestations of the exchange of genetic material occurring during homologous recombination. CO number varies little at around two per chromosome pair, and they tend to be evenly spaced on chromosomes. Thus, CO number and distribution are very tightly controlled. However, the mechanisms underlying these controls are very poorly understood. In this study, we identified a regulatory pathway of meiotic recombination. We show that this pathway does not regulate the amount of recombination events per se, but instead controls their localisation, as when it is defective, CO events cluster together in a few regions of the genome, leading to bivalent shortage and progeny aneuploidy with incorrect numbers of chromosomes. This regulatory pathway is a posttranslational protein modification system called neddylation (or rubylation in plants), known to be required for numerous cellular processes in eukaryotes. We identify an enzyme of the neddylation complex as a major regulator of meiotic recombination in Arabidopsis and show that this process may be also conserved in mammals.