rad-51 downregulation redirects DNA repair and preserves genome stability in FANCD2-deficient Caenorhabditis elegans

Abstract Background Fanconi anemia is a rare genomic instability syndrome associated with congenital abnormalities and cancer predisposition. These alterations are mainly due to deficiencies in DNA repair mechanisms. The Fanconi anemia pathway is evolutionarily conserved, allowing functional studies in model organisms like Caenorhabditis elegans, where it promotes and executes error-free homologous-recombination over mutagenic non-homologous-end-joining; fcd-2 (FANCD2 ortholog) plays a key role in this regulation to preserve genome stability. In this study, we report that the choice of DNA repair pathway for resolving double-strand-breaks is influenced by the expression level of rad-51, a key component of the Fanconi anemia pathway that plays a central role in homologous strand exchange during the recombination. Results We show that rad-51 downregulation increases the efficiency of homologous-recombination and the crossovers formation. We also demonstrate that the downregulation of rad-51 decreases developmental and meiotic defects in fcd-2 mutants as well as it reduces chromosome aggregation in fcd-2-deficient germ cells. Conclusions Together, these finding reveal a novel role for RAD-51 suggesting that the rad-51 expression level modulates the balance between homologous-recombination and non-homologous-end-joining preserving genome stability.