Meiotic recombination requires the formation and repair of genome-wide, programmed double-stranded breaks (DSBs). Repair of meiotic DSBs requires homologous recombination (HR), an error-free repair pathway required for crossover formation. Accordingly, error-prone pathways such as non-homologous end joining (NHEJ) are not favored during meiosis due to their propensity for generating mutations and their inability to form chiasmata. How error prone repair pathways are suppressed during meiosis is not well understood. Here, we demonstrate a role of for Mi2, the core ATPase subunit of the NuRD chromatin remodeling complex, in coordinating the repair of DSBs and maintaining genomic stability through multiple mechanisms. Our data reveal that the conserved Mi2 homologs CHD-3 and LET-418 promote HR, though in their absence, NHEJ is engaged as a secondary DNA repair mechanism to prevent persisting damage in gametes. In support of this, our findings indicate that a population of DSBs are repaired via NHEJ in situations with compromised LET-418 activity. Though HR mechanisms remain partially intact in
let-418 mutants, their germ lines possess multiple defects including increased corpses and presence of structurally abnormal chromosomes in oocytes. These data are corroborated by molecular evidence wherein
let-418 mutants have elevated expression of several NHEJ components, indicating a role for NuRD in the transcriptional regulation of repair genes during meiosis. Intriguing, our data also reveal that loss of LET-418 leads to upregulation of HR machinery, which we attribute to increased genomic stress in mitotically dividing germ cells, and we are currently investigating the causes and consequences of this. As these genes involved in these processes are highly conserved throughout eukaryotes, our findings have implications for understanding how Mi2 may contribute to the prevention of human disease states such as infertility and cancer.