Altering the dosage of meiotic crossover-associated RING finger proteins affects crossover number and interference in Drosophila.

Crossovers play a critical role in ensuring correct reductional segregation of homologous chromosomes in the first meiotic division. Crossing over is initiated by formation of DNA double-strand breaks (DSBs), but the number of DSBs is greater than the number of crossovers. Which recombination sites become crossovers, versus being repaired as noncrossovers, is not random, but is subject to several crossover patterning phenomena. One current model for crossover designation proposes that crossover-associated RING finger proteins (CORs) undergo the biophysical process of coarsening, in which larger accumulations continue to get larger, destining those sites to become noncrossovers, and smaller accumulations go away, resulting in those sites being repair as noncrossovers. Genetic and cytological studies of the three CORs in Drosophila melanogaster, Vilya, Narya, and Nenya, are consistent with this model. We tested another prediction of the coarsening model, that differences in COR dosage will lead to differences in crossover number. In females heterozygous for a deletion of vilya, significantly fewer double-crossovers are observed. Conversely, crossovers are elevated in females carrying a duplication of vilya and in females coordinately overexpressing all three CORs. These findings lend additional support to the proposal that crossover designation in D. melanogaster occurs through coarsening of COR proteins within the synaptonemal complex.