Chromosome Cohesion Established by Rec8-Cohesin in Fetal Oocytes Is Maintained without Detectable Turnover in Oocytes Arrested for Months in Mice.
Chromosome Cohesion Established by Rec8-Cohesin in Fetal Oocytes Is Maintained without Detectable Turnover in Oocytes Arrested for Months in Mice.
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DOI：
10.1016/j.cub.2015.12.073
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发表时间：
2016-03-07
期刊：
影响因子：
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通讯作者：
Tachibana-Konwalski K
中科院分区：
文献类型：
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作者：
Burkhardt S;Borsos M;Szydlowska A;Godwin J;Williams SA;Cohen PE;Hirota T;Saitou M;Tachibana-Konwalski K
在有丝分裂和减数分裂中，由内聚蛋白复合物介导的姐妹染色单体内聚对染色体分离至关重要。含有rec8的内聚蛋白与Smc3/Smc1α或Smc3/Smc1β结合，在哺乳动物减数分裂中维持二价内聚。在女性中，减数分裂DNA复制和重组发生在胎儿卵母细胞中。出生后，卵母细胞停留在长时间的支配阶段，直到被招募成长为成熟的卵母细胞，在排卵时分裂。内聚力如何维持在冻结卵母细胞仍然是一个关键的问题，与母亲年龄相关的非整倍体。理论上，内聚蛋白的周转可以使卵母细胞内聚再生。在酵母和无脊椎动物中存在复制后内聚建立机制的证据。在小鼠胎儿卵母细胞中，在重组过程中，内聚蛋白装载因子Nipbl/Scc2定位于染色体轴。另一种选择是，在没有周转的情况下保持内聚。与此一致的是，内聚维持不需要Smc1β的转录，但与Rec8不同的是，Smc1β不需要建立二价内聚。在数周的卵母细胞生长过程中，Rec8保持内聚而不发生周转。这种情况是否适用于数月或数十年的逮捕还不得而知。在这里，我们通过TEV切割和活细胞成像测试了Rec8是否在被阻滞的小鼠卵母细胞中被激活以建立内聚。使用他莫昔芬诱导的Cre，在胎儿卵母细胞DNA复制过程中激活Rec8，建立内聚。相反，当他莫昔芬激活卵母细胞中的Rec8时，尽管内聚蛋白合成，但没有检测到新的内聚蛋白。我们得出的结论是，在胎儿卵母细胞中建立的内聚可以维持数月，而在指令捕获的卵母细胞中没有可检测到的周转。这意味着女性的生育能力取决于在子宫内建立凝聚力的黏结蛋白的寿命。re8介导的染色体内聚在胎儿卵母细胞中建立，二价内聚在被阻滞的卵母细胞中没有可检测到的更新，不可逆的内聚损失是年龄相关的染色体错分离的基础，染色体内聚是如何在被阻滞数月或数十年的女性生殖细胞中维持的，目前尚不清楚。Burkhardt等人的研究表明，内聚是在胎儿卵母细胞中建立起来的，在出生后的几个月里，内聚一直保持着，没有明显的更新。这表明，卵母细胞无法更新凝聚力有助于母亲年龄相关的三体。
Sister chromatid cohesion mediated by the cohesin complex is essential for chromosome segregation in mitosis and meiosis. Rec8-containing cohesin, bound to Smc3/Smc1α or Smc3/Smc1β, maintains bivalent cohesion in mammalian meiosis. In females, meiotic DNA replication and recombination occur in fetal oocytes. After birth, oocytes arrest at the prolonged dictyate stage until recruited to grow into mature oocytes that divide at ovulation. How cohesion is maintained in arrested oocytes remains a pivotal question relevant to maternal age-related aneuploidy. Hypothetically, cohesin turnover regenerates cohesion in oocytes. Evidence for post-replicative cohesion establishment mechanism exists, in yeast and invertebrates. In mouse fetal oocytes, cohesin loading factor Nipbl/Scc2 localizes to chromosome axes during recombination. Alternatively, cohesion is maintained without turnover. Consistent with this, cohesion maintenance does not require Smc1β transcription, but unlike Rec8, Smc1β is not required for establishing bivalent cohesion. Rec8 maintains cohesion without turnover during weeks of oocyte growth. Whether the same applies to months or decades of arrest is unknown. Here, we test whether Rec8 activated in arrested mouse oocytes builds cohesion revealed by TEV cleavage and live-cell imaging. Rec8 establishes cohesion when activated during DNA replication in fetal oocytes using tamoxifen-inducible Cre. In contrast, no new cohesion is detected when Rec8 is activated in arrested oocytes by tamoxifen despite cohesin synthesis. We conclude that cohesion established in fetal oocytes is maintained for months without detectable turnover in dictyate-arrested oocytes. This implies that women’s fertility depends on the longevity of cohesin proteins that established cohesion in utero. Rec8-mediated chromosome cohesion is established in fetal oocytes Bivalent cohesion is maintained without detectable turnover in arrested oocytes Irreversible cohesin loss underlies age-related chromosome missegregation How chromosome cohesion is maintained in female germ cells arrested for months or decades is poorly understood. Burkhardt et al. show that cohesion is built in fetal oocytes and after birth is maintained without detectable renewal for months. This implies that the oocyte’s inability to renew cohesion contributes to maternal age-related trisomies.