Mammalian oocytes can be very long-lived cells and thereby are very likely to encounter DNA damage during their lifetime. Defective DNA repair may result in oocytes that are developmentally incompetent or give rise to progeny with congenital disorders. During oocyte maturation, damaged DNA is repaired primarily by non-homologous end joining (NHEJ) or homologous recombination (HR). Although these repair pathways have been studied extensively, the associated DNA synthesis is poorly characterized. Here, using porcine oocytes, we demonstrate that the DNA synthesis machinery is present during oocyte maturation and dynamically recruited to sites of DNA damage. DNA polymerase δ is identified as being crucial for oocyte DNA synthesis. Furthermore, inhibiting synthesis causes DNA damage to accumulate and delays the progression of oocyte maturation. Importantly, inhibition of the spindle assembly checkpoint (SAC) bypassed the delay of oocyte maturation caused by DNA synthesis inhibition. Finally, we found that ∼20% of unperturbed oocytes experienced spontaneously arising damage during maturation. Cumulatively, our findings indicate that oocyte maturation requires damage-associated DNA synthesis that is monitored by the SAC. This article has an associated First Person interview with the first author of the paper.

中文翻译：

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局部 DNA 合成对于卵母细胞成熟过程中的 DNA 修复至关重要。

哺乳动物卵母细胞可以是非常长寿的细胞，因此很可能在其一生中遇到 DNA 损伤。有缺陷的 DNA 修复可能导致卵母细胞发育无能或产生先天性疾病的后代。在卵母细胞成熟过程中，受损的 DNA 主要通过非同源末端连接 (NHEJ) 或同源重组 (HR) 进行修复。尽管已经对这些修复途径进行了广泛的研究，但相关的 DNA 合成的特征却很差。在这里，我们使用猪卵母细胞，证明 DNA 合成机制在卵母细胞成熟过程中存在，并动态地招募到 DNA 损伤部位。DNA聚合酶δ被鉴定为对卵母细胞DNA合成至关重要。此外，抑制合成会导致 DNA 损伤累积并延迟卵母细胞成熟的进程。重要的是，纺锤体组装检查点 (SAC) 的抑制绕过了由 DNA 合成抑制引起的卵母细胞成熟延迟。最后，我们发现约 20% 未受干扰的卵母细胞在成熟过程中经历了自发性损伤。总的来说，我们的研究结果表明，卵母细胞成熟需要 SAC 监测的与损伤相关的 DNA 合成。本文与该论文的第一作者进行了相关的第一人称采访。