Meiotic DNA joint molecule resolution depends on Nse5-Nse6 of the Smc5-Smc6 holocomplex

作者：Wehrkamp Richter Sophie; Hyppa Randy W; Prudden John; Smith Gerald R^*; Boddy Michael N

来源：Nucleic Acids Research, 2012, 40(19): 9633-9646.

DOI：10.1093/nar/gks713

Faithful chromosome segregation in meiosis is crucial to form viable, healthy offspring and in most species, it requires programmed recombination 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 generate crossovers and thereby allow proper chromosome 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 intermediates (DNA joint molecules) resembling HJs that accumulate in mus81 delta cells. Elimination of Rec12 nearly completely rescues the meiotic defects of nse6 delta and mus81 delta single mutants and partially rescues nse6 delta mus81 delta double mutants, indicating that these factors act after DNA double-strand break formation. Likewise, expression of the bacterial HJ resolvase RusA partially rescues the defects of nse6 delta, mus81 delta and nse6 delta mus81 delta mitotic cells, as well as the meiotic defects of nse6 delta and mus81 delta 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.

• 出版日期2012-10