Sun Ming-Hong, Yang Mo, Xie Feng-Yun, Wang Wei, Zhang Lili, Shen Wei, Yin Shen, Ma Jun-Yu
College of Animal Science and Technology, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, China.
Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
PLoS One. 2017 Jan 18;12(1):e0170308. doi: 10.1371/journal.pone.0170308. eCollection 2017.
As a gamete, oocyte needs to maintain its genomic integrity and passes this haploid genome to the next generation. However, fully-grown mouse oocyte cannot respond to DNA double-strand breaks (DSBs) effectively and it is also unable to repair them before the meiosis resumption. To compensate for this disadvantage and control the DNA repair events, oocyte needs the cooperation with its surrounding cumulus cells. Recently, evidences have shown that nuclear actin filament formation plays roles in cellular DNA DSB repair. To explore whether these nuclear actin filaments are formed in the DNA-damaged oocytes, here, we labeled the filament actins in denuded oocytes (DOs) and cumulus-enclosed oocytes (CEOs). We observed that the nuclear actin filaments were formed only in the DNA-damaged CEOs, but not in DOs. Formation of actin filaments in the nucleus was an event downstream to the DNA damage response. Our data also showed that the removal of cumulus cells led to a reduction in the nuclear actin filaments in oocytes. Knocking down of the Adcy1 gene in cumulus cells did not affect the formation of nuclear actin filaments in oocytes. Notably, we also observed that the nuclear actin filaments in CEOs could be induced by inhibition of gap junctions. From our results, it was confirmed that DNA DSBs induce the nuclear actin filament formation in oocyte and which is controlled by the cumulus cells.
作为一种配子，卵母细胞需要维持其基因组完整性，并将这个单倍体基因组传递给下一代。然而，完全成熟的小鼠卵母细胞不能有效地应对DNA双链断裂（DSB），并且在减数分裂恢复之前也无法修复它们。为了弥补这一缺陷并控制DNA修复事件，卵母细胞需要与其周围的卵丘细胞合作。最近，有证据表明核肌动蛋白丝的形成在细胞DNA DSB修复中发挥作用。为了探究这些核肌动蛋白丝是否在DNA受损的卵母细胞中形成，在此，我们对裸卵（DO）和卵丘包裹的卵母细胞（CEO）中的丝状肌动蛋白进行了标记。我们观察到，核肌动蛋白丝仅在DNA受损的CEO中形成，而在DO中未形成。细胞核中肌动蛋白丝的形成是DNA损伤反应下游的一个事件。我们的数据还表明，去除卵丘细胞会导致卵母细胞中核肌动蛋白丝减少。敲低卵丘细胞中的Adcy1基因并不影响卵母细胞中核肌动蛋白丝的形成。值得注意的是，我们还观察到，抑制缝隙连接可以诱导CEO中的核肌动蛋白丝形成。从我们的结果可以证实，DNA DSB会诱导卵母细胞中核肌动蛋白丝的形成，并且这一过程受卵丘细胞控制。
