Data from: The kinetochore prevents centromere-proximal crossover recombination during meiosis

During meiosis, crossover recombination is essential to link homologous chromosomes and drive 22 faithful chromosome segregation. Crossover recombination is non-random across the genome, 23 and centromere-proximal crossovers are associated with an increased risk of aneuploidy, 24 including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub- 25 complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers 26 in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the 27 Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents 28 meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. 29 The Ctf19 complex independently drives the enrichment of cohesin throughout the broader 30 pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the 31 kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer 32 of functionality by which the kinetochore prevents the incidence of chromosome segregation 33 errors that generate aneuploid gametes.

减数分裂过程中，交叉重组（crossover recombination）对于连接同源染色体并保障染色体精准分离不可或缺。交叉重组在基因组中的分布并非随机，着丝粒近端的交叉重组与非整倍体风险升高密切相关，其中就包括人类的21三体综合征。本研究鉴定出保守的Ctf19/CCAN动粒亚复合物，它是酿酒酵母中最小化潜在有害的着丝粒近端交叉重组的核心调控因子。我们揭示了Ctf19复合物通过多层级机制抑制着丝粒周缘重组，该调控覆盖不同的染色体距离区间。Ctf19复合物可阻止着丝粒近端区域发生减数分裂DNA断裂——这是重组过程的起始事件。此外，Ctf19复合物可独立介导黏连蛋白（cohesin）在更广泛的着丝粒周缘区域富集，以此抑制交叉重组，但并不影响DNA断裂的发生。动粒的这一非经典功能，可定义一个对交叉重组具有抗性的染色体结构域，这为动粒新增了一层调控功能：通过该功能，动粒可减少产生非整倍体配子的染色体分离错误的发生概率。