PDF(Pubmed)
Abstract：
In dividing cells, accurate chromosome segregation depends on sister chromatid cohesion, protein linkages that are established during DNA replication. Faithful chromosome segregation in oocytes requires that cohesion, first established in S phase, remain intact for days to decades, depending on the organism. Premature loss of meiotic cohesion in oocytes leads to the production of aneuploid gametes and contributes to the increased incidence of meiotic segregation errors as women age (maternal age effect). The prevailing model is that cohesive linkages do not turn over in mammalian oocytes. However, we have previously reported that cohesion-related defects arise in Drosophila oocytes when individual cohesin subunits or cohesin regulators are knocked down after meiotic S phase. Here, we use two strategies to express a tagged cohesin subunit exclusively during mid-prophase in Drosophila oocytes and demonstrate that newly expressed cohesin is used to form de novo linkages after meiotic S phase. Cohesin along the arms of oocyte chromosomes appears to completely turn over within a 2-day window during prophase, whereas replacement is less extensive at centromeres. Unlike S-phase cohesion establishment, the formation of new cohesive linkages during meiotic prophase does not require acetylation of conserved lysines within the Smc3 head. Our findings indicate that maintenance of cohesion between S phase and chromosome segregation in Drosophila oocytes requires an active cohesion rejuvenation program that generates new cohesive linkages during meiotic prophase.
摘要：
在分裂的细胞中，准确的染色体分离取决于姐妹染色单体的凝聚力，在DNA复制过程中建立的蛋白质连接。卵母细胞中忠实的染色体分离需要凝聚力，首先建立在S阶段，保持完好无损几天到几十年，取决于有机体。卵母细胞中减数分裂内聚力的过早丧失导致非整倍体配子的产生，并随着女性年龄的增长（母亲年龄的影响）导致减数分裂分离错误的发生率增加。流行的模型是内聚连接不会在哺乳动物卵母细胞中翻转。然而,我们以前曾报道过,当减数分裂S期后单个粘附素亚基或粘附素调节因子被击倒时,果蝇卵母细胞会出现内聚相关缺陷.这里,我们使用两种策略仅在果蝇卵母细胞的前期中期表达标记的粘附蛋白亚基，并证明新表达的粘附蛋白可用于在减数分裂S期后形成从头连接。在前期，沿着卵母细胞染色体臂的Cohesin似乎在2天内完全翻转，而在着丝粒的置换不那么广泛。与S阶段内聚建立不同，减数分裂前期形成新的内聚键不需要Smc3头部内保守赖氨酸的乙酰化。我们的发现表明，果蝇卵母细胞中S期和染色体分离之间的内聚力的维持需要一个积极的内聚复兴计划，该计划在减数分裂前期产生新的内聚联系。
