DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint.
DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint.
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DOI：
10.1038/ncomms9553
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发表时间：
2015-11-02
影响因子：
16.6
通讯作者：
Jones KT
中科院分区：
文献类型：
--
作者：
Collins JK;Lane SIR;Merriman JA;Jones KT
在减数分裂过程中，母体DNA的广泛破坏会导致不孕、出生缺陷和流产。然而，目前尚不清楚完全成熟的卵母细胞是否有机制防止产生DNA受损的胚胎。在这里，我们展示了DNA损伤激活了涉及纺锤体组装检查点(SAC)的途径，以响应化学诱导的双链断裂、UVB和电离辐射。DNA损伤可以发生在核膜破裂之前或之后，并有效地阻止后期促进复合体的活动，从而形成成熟的卵子。这与体细胞不同，体细胞中的DNA损伤不会影响有丝分裂的进程。然而，它揭示了减数分裂SAC的第二个功能，在检测微管-动粒错误的背景下，该功能迄今在哺乳动物卵母细胞中被标记为弱或无效。我们认为，它在检测DNA损伤中的重要作用为它在哺乳动物雌性减数分裂中的生物学作用提供了新的线索。减数分裂过程中母体DNA的损伤可能会导致出生缺陷、流产或不育。在这里，作者表明，纺锤体组装检查点可以通过阻止后期促进复合体活性和阻止减数分裂I中的卵母细胞来响应卵母细胞的DNA损伤。
Extensive damage to maternal DNA during meiosis causes infertility, birth defects and abortions. However, it is unknown if fully grown oocytes have a mechanism to prevent the creation of DNA-damaged embryos. Here we show that DNA damage activates a pathway involving the spindle assembly checkpoint (SAC) in response to chemically induced double strand breaks, UVB and ionizing radiation. DNA damage can occur either before or after nuclear envelope breakdown, and provides an effective block to anaphase-promoting complex activity, and consequently the formation of mature eggs. This contrasts with somatic cells, where DNA damage fails to affect mitotic progression. However, it uncovers a second function for the meiotic SAC, which in the context of detecting microtubule–kinetochore errors has hitherto been labelled as weak or ineffectual in mammalian oocytes. We propose that its essential role in the detection of DNA damage sheds new light on its biological purpose in mammalian female meiosis. Damage to maternal DNA during meosis can lead to birth defects, abortion or infertility. Here, the authors show that the spindle assembly checkpoint can respond to DNA damage in oocytes by blocking anaphase promoting complex activity and arresting oocytes in meiosis I.