AXR1 protein, an important player controlling the localization of chromosome exchanges during gamete formation in Arabidopsis thaliana

Meiotic crossovers (COs) (reciprocal exchange of chromosome fragments) are an essential tool to reassociate genetic traits. This tool is used by breeders to develop and improve plant varieties. The number and position of crossovers along the chromosomes is finely regulated. The MeioMe team aims to elucidate the mechanisms responsible for these controls using the model plant Arabidopsis thaliana. They found that the neddylation protein AXR1 probably indirectly controls the position of crossovers on the genome.

During meiosis, crossovers are essential to produce haploid spores and viable gametes. Moreover, crossovers allow to reassociate genetic characters. The number and location of COs along the chromosomes are finely regulated.  A inaprpropriate localization or their absence lead to the formation of non-viable aneuploid gametes (sterility) or abnormalities in the offsprings (trisomy 21, Klinefelter syndrome).  

The MeioMe team and its collaborator identified the AXR1 protein as an important player controlling COs localization in Arabidopsis thaliana. This protein controls a pathway of post-translational modification of proteins (neddylation).

In an axr1 mutant, the number of crossovers is identical to that found in a wild-type plant. However, instead of being evenly distributed along the chromosomes, COs are clustered at the ends of the chromosomes. The early stages of meiotic recombination (formation of DNA double-strand breaks and repair) are proceeding normally. However, the chromosome pairing and synapsis steps are severely affected while neither the location of chromosomes in the nucleus nor the positioning of telomeres seems to be disturbed. We wondered if these changes in crossover location could reflect a change in the level of DNA methylation along the chromosomes. Indeed, in the absence of the AXR1 protein, DNA extracted from meiocytes is hypermethylated compared to DNA from wild type meiocytes. This deregulation of DNA methylation is global since it is also found in somatic cells of the plant. However, when the axr1 mutation is combined with a mutation that inactivates one or other of the three DNA methylation pathways, the meiocyte DNA is much less methylated than the DNA extracted from wild-type meiocytes, but the crossovers remain delocalized at the chromosome ends. Thus in this mutant context it is not DNA methylation that influences the position of meiotic crossover events, these two phenomena are uncoupled. 

The team is looking for the target of the neddylation machinery that is modified during meiosis. The identification of this target would allow us to understand the mechanism that regulates the positioning of chromsomes during meiosis and thus possibly use it to direct crossovers in regions with few recombinations.