The DNA damage response in mammalian oocytes.
The DNA damage response in mammalian oocytes.
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DOI：
10.3389/fgene.2013.00117
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发表时间：
2013
影响因子：
3.7
通讯作者：
Marangos P
中科院分区：
文献类型：
--
作者：
Carroll J;Marangos P
DNA损伤是挑战所有细胞的最常见的侮辱之一。为了应对，一种复杂的分子和细胞反应已经进化到感知、反应和纠正损伤。这可以维持正常细胞存活所必需的DNA保真度，并防止可能导致肿瘤形成的基因组不稳定。在卵母细胞的情况下，DNA损伤的影响不是肿瘤形成，而是维持生育能力。哺乳动物的卵母细胞特别容易受到DNA的破坏，因为从生理上讲，它们可能会在卵巢中休眠多年(人类为40岁)，直到它们得到生长的刺激并获得受精的能力。这意味着，在一些生物中，例如人类，卵母细胞面临着数十年来累积遗传损伤的危险。因此，检测和修复DNA损伤的能力对于维持生殖所需的卵母细胞供应至关重要。因此，如果不能抵抗卵母细胞中的DNA损伤，可能会导致胚胎出现严重的异常，这些异常可能会以突变的形式传播给下一代，从而出现遗传性疾病。尽管DNA损伤对胚胎的生殖能力和遗传保真度有潜在的影响，但卵母细胞用于监测和修复这种侮辱的机制直到最近才得到很大程度的探索。在这里，我们综述了哺乳动物卵母细胞对DNA损伤反应的不同方面。具体地说，我们讨论了从胚胎到成年期以及整个卵母细胞发育过程中的卵母细胞DNA损伤反应。
DNA damage is one of the most common insults that challenge all cells. To cope, an elaborate molecular and cellular response has evolved to sense, respond to and correct the damage. This allows the maintenance of DNA fidelity essential for normal cell viability and the prevention of genomic instability that can lead to tumor formation. In the context of oocytes, the impact of DNA damage is not one of tumor formation but of the maintenance of fertility. Mammalian oocytes are particularly vulnerable to DNA damage because physiologically they may lie dormant in the ovary for many years (>40 in humans) until they receive the stimulus to grow and acquire the competence to become fertilized. The implication of this is that in some organisms, such as humans, oocytes face the danger of cumulative genetic damage for decades. Thus, the ability to detect and repair DNA damage is essential to maintain the supply of oocytes necessary for reproduction. Therefore, failure to confront DNA damage in oocytes could cause serious anomalies in the embryo that may be propagated in the form of mutations to the next generation allowing the appearance of hereditary disease. Despite the potential impact of DNA damage on reproductive capacity and genetic fidelity of embryos, the mechanisms available to the oocyte for monitoring and repairing such insults have remained largely unexplored until recently. Here, we review the different aspects of the response to DNA damage in mammalian oocytes. Specifically, we address the oocyte DNA damage response from embryonic life to adulthood and throughout oocyte development.