Pairing and synapsis of homologous chromosomes during meiosis is crucial for producing genetically normal gametes and is dependent upon repair of SPO11-induced double-strand breaks (DSBs) by homologous recombination. To prevent transmission of genetic defects, diverse organisms have evolved mechanisms to eliminate meiocytes containing unrepaired DSBs or unsynapsed chromosomes. Here we show that the CHK2 (CHEK2)-dependent DNA damage checkpoint culls not only recombination-defective mouse oocytes but also SPO11-deficient oocytes that are severely defective in homolog synapsis. The checkpoint is triggered in oocytes that accumulate a threshold level of spontaneous DSBs (∼10) in late prophase I, the repair of which is inhibited by the presence of HORMAD1/2 on unsynapsed chromosome axes. Furthermore, Hormad2 deletion rescued the fertility of oocytes containing a synapsis-proficient, DSB repair-defective mutation in a gene (Trip13) required for removal of HORMADs from synapsed chromosomes, suggesting that many meiotic DSBs are normally repaired by intersister recombination in mice.

减数分裂过程中同源染色体的配对和突触对于产生遗传上正常的配子至关重要，并且取决于通过同源重组对SPO11诱导的双链断裂（DSB）的修复。为了防止遗传缺陷的传播，各种各样的生物体已经进化出消除含有未修复的DSB或未突触的染色体的减数分裂细胞的机制。在这里，我们显示了CHK2（CHEK2）依赖的DNA损伤检查点不仅剔除重组缺陷型小鼠卵母细胞，而且还剔除在同源突触中严重缺陷的SPO11缺陷型卵母细胞。检查点是在卵母细胞中触发的，卵母细胞在前期I晚期积累了自发DSB的阈值水平（约10），其修复受到未突触染色体轴上HORMAD1 / 2的存在的抑制。此外，Hormad2缺失挽救了卵母细胞的生育能力，该卵母细胞含有从突触染色体中除去HORMADs所需的基因（Trip13）中具有突触能力的，DSB修复缺陷型突变，这表明许多减数分裂的DSB通常可以通过小鼠间的重组来修复。