Meiotic DNA joint molecule resolution depends on

Faithful chromosome segregation in meiosis is crucial to form viable, healthy offspring and in most species, it requires programmed recombin-ation between homologous chromosomes. In fission yeast, meiotic recombination is initiated by Rec12 (Spo11 homolog) and generates single Holliday junction (HJ) intermediates, which are resolved by the Mus81–Eme1 endonuclease to gen-erate crossovers and thereby allow proper chromo-some segregation. Although Mus81 contains the active site for HJ resolution, the regulation of Mus81–Eme1 is unclear. In cells lacking Nse5– Nse6 of the Smc5–Smc6 genome stability complex, we observe persistent meiotic recombination inter-mediates (DNA joint molecules) resembling HJs that accumulate in mus81D cells. Elimination of Rec12 nearly completely rescues the meiotic defects of nse6D and mus81D single mutants and partially rescues nse6D mus81D double mutants, indicating that these factors act after DNA double-strand break formation. Likewise, expression of the bacter-ial HJ resolvase RusA partially rescues the defects of nse6D, mus81D and nse6D mus81D mitotic cells, as well as the meiotic defects of nse6D and mus81D cells. Partial rescue likely reflects the accumulation of structures other than HJs, such as hemicatenanes, and an additional role for Nse5– Nse6 most prominent during mitotic growth. Our results indicate a regulatory role for the Smc5–Smc6 complex in HJ resolution via Mus81– Eme1