Ronin influences the DNA damage response in pluripotent stem cells.

Ronin influences the DNA damage response in pluripotent stem cells.
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DOI:
10.1016/j.scr.2017.06.014
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发表时间:
2017-08
期刊:
影响因子:
1.2
通讯作者:
Zwaka TP
Zwaka TP
中科院分区:
医学4区
文献类型:
--
作者:
Seifert BA;Dejosez M;Zwaka TP

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早期的哺乳动物胚胎细胞必须保持一个特别强大的DNA修复系统,因为在这个发育阶段的突变会对生物体产生不利影响。修复系统如何被调整以满足如此高的要求在很大程度上是未知的,但它可能涉及转录调控。Ronin(Thap 11)是一种转录调节因子,负责多能细胞中的重要程序。在这里,我们报告说,这种蛋白质也调节这些细胞的DNA损伤反应。我们发现,有条件的Ronin敲除敏感的胚胎干细胞(ESCs)与Atr通路激活和G2/M期阻滞的UV-C诱导的DNA损伤。Ronin结合并调节编码几种DNA修复因子的基因,包括Gtf 2 h4和Rad 18,为这种表型提供了潜在的机制。我们的研究结果表明,早期胚胎独特的DNA修复要求不是由静态系统满足的,而是通过高度调节的过程。
Early mammalian embryonic cells must maintain a particularly robust DNA repair system, as mutations at this developmental point have detrimental consequences for the organism. How the repair system can be tuned to fulfill such elevated requirements is largely unknown, but it may involve transcriptional regulation. Ronin (Thap11) is a transcriptional regulator responsible for vital programs in pluripotent cells. Here, we report that this protein also modulates the DNA damage response of such cells. We show that conditional Ronin knockout sensitizes embryonic stem cells (ESCs) to UV-C-induced DNA damage in association with Atr pathway activation and G2/M arrest. Ronin binds to and regulates the genes encoding several DNA repair factors, including Gtf2h4 and Rad18, providing a potential mechanism for this phenotype. Our results suggest that the unique DNA repair requirements of the early embryo are not met by a static system, but rather via highly regulated processes.
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