A meiotic XPF-ERCC1-like complex recognizes joint molecule recombination intermediates to promote crossover formation

Meiotic crossover formation requires the stabilization of early recombination intermediates by a set of proteins and occurs within the environment of the chromosome axis, a structure important for the regulation of meiotic recombination events. The molecular mechanisms underlying and connecting crossover recombination and axis localization are elusive. Here, we identified the ZZS (Zip2–Zip4–Spo16) complex, required for crossover formation, which carries two distinct activities: one provided by Zip4, which acts as hub through physical interactions with components of the chromosome axis and the crossover machinery, and the other carried by Zip2 and Spo16, which preferentially bind branched DNA molecules in vitro. We found that Zip2 and Spo16 share structural similarities to the structure-specific XPF–ERCC1 nuclease, although it lacks endonuclease activity. The XPF domain of Zip2 is required for crossover formation, suggesting that, together with Spo16, it has a noncatalytic DNA recognition function. Our results suggest that the ZZS complex shepherds recombination intermediates toward crossovers as a dynamic structural module that connects recombination events to the chromosome axis. The identification of the ZZS complex improves our understanding of the various activities required for crossover implementation and is likely applicable to other organisms, including mammals.减数分裂交叉的形成需要一系列蛋白质稳定早期重组中间体，且发生于染色体轴的结构环境中——该结构对减数分裂重组事件的调控至关重要。目前，介导交叉重组与染色体轴定位并将二者相连的分子机制仍不甚明晰。本研究鉴定出了ZZS复合体（Zip2–Zip4–Spo16），其为减数分裂交叉形成所必需，且具备两种截然不同的活性：其一由Zip4介导，作为枢纽通过与染色体轴组分及交叉形成相关分子机器发生物理相互作用发挥功能；其二由Zip2与Spo16承载，二者在体外可优先结合分支DNA分子。我们发现，尽管Zip2与Spo16缺乏核酸内切酶活性，但其结构与结构特异性核酸酶XPF–ERCC1存在相似性。Zip2的XPF结构域对于减数分裂交叉形成必不可少，这提示其与Spo16共同发挥非催化性的DNA识别功能。本研究结果表明，ZZS复合体作为连接重组事件与染色体轴的动态结构模块，可引导重组中间体向交叉产物方向生成。ZZS复合体的鉴定加深了我们对交叉形成所需各项活性的理解，且该结论大概率可推广至包括哺乳动物在内的其他生物。