MCM8/9 is a complex involved in homologous recombination (HR) repair pathway. MCM8/9 dysfunction can cause genome instability and result in primary ovarian insufficiency (POI). However, the mechanism underlying these effects is largely unknown. Here, we report crystal structures of the N-terminal domains (NTDs) of MCM8 and MCM9, and build a ring-shaped NTD structure based on a 6.6 Å resolution cryoelectron microscopy map. This shows that the MCM8/9 complex forms a 3:3 heterohexamer in an alternating pattern. A positively charged DNA binding channel and a putative ssDNA exit pathway for fork DNA unwinding are revealed. Based on the atomic model, the potential effects of the clinical POI mutants are interpreted. Surprisingly, the zinc-finger motifs are found to be capable of binding an iron atom as well. Overall, our results provide a model for the formation of the MCM8/9 complex and provide a path for further studies.

MCM8/9 是一种参与同源重组 (HR) 修复途径的复合物。MCM8/9 功能障碍可导致基因组不稳定并导致原发性卵巢功能不全 (POI)。然而，这些影响背后的机制在很大程度上是未知的。在这里，我们报告了 MCM8 和 MCM9 的 N 端域 (NTD) 的晶体结构，并基于 6.6 Å 分辨率的低温电子显微镜图构建了一个环状 NTD 结构。这表明 MCM8/9 复合物以交替模式形成 3:3 异六聚体。揭示了一个带正电荷的 DNA 结合通道和一个假定的 ssDNA 退出途径，用于叉 DNA 解旋。基于原子模型，解释了临床 POI 突变体的潜在影响。令人惊讶的是，发现锌指基序也能够结合铁原子。全面的，