Narya, a RING finger domain-containing protein, is required for meiotic DNA double-strand break formation and crossover maturation in Drosophila melanogaster

Meiotic recombination, which is necessary to ensure that homologous chromosomes segregate properly, begins with the induction of meiotic DNA double-strand breaks (DSBs) and ends with the repair of a subset of those breaks into crossovers. Here we investigate the roles of two paralogous genes, CG12200 and CG31053, which we have named Narya and Nenya, respectively, due to their relationship with a structurally similar protein named Vilya. We find that narya recently evolved from nenya by a gene duplication event, and we show that these two RING finger domain-containing proteins are functionally redundant with respect to a critical role in DSB formation. Narya colocalizes with Vilya foci, which are known to define recombination nodules, or sites of crossover formation. A separation-of-function allele of narya retains the capacity for DSB formation but cannot mature those DSBs into crossovers. We further provide data on the physical interaction of Narya, Nenya and Vilya, as assayed by the yeast two-hybrid system. Together these data support the view that all three RING finger domain-containing proteins function in the formation of meiotic DNA DSBs and in the process of crossing over. Author summary Errors in chromosome segregation during meiosis are the leading cause of miscarriages and can result in genetic abnormalities like Down syndrome or Turner syndrome. For chromosomes to segregate faithfully, they must recombine with their homolog during the early steps of meiosis. An essential component of the process of meiotic recombination is creating the lesions (double-strand breaks, DSBs) that are required to form a crossover with the homologous chromosome. Crossovers are required to ensure chromosomes segregate properly at the first meiotic division. In this study we have identified two genes, narya and nenya, that are essential in DSB formation. We found that narya arose from a duplication of nenya, and these two genes are functionally redundant. In addition to its role in DSB formation, narya also plays a role in processing DSBs into crossovers. Strengthening our knowledge about the mechanism by which Narya both creates DSBs and processes them into crossovers will lead to a better understanding of the process of meiotic chromosome segregation not only in flies but many other organisms, as these genes have homologs in yeast, worms, plants, mice and humans.