The reactivation of X-linked genes is observed in some primary breast tumors. Two active X chromosomes are also observed in female embryonic stem cells (ESCs), but whether double doses of X-linked genes affect DNA repair efficiency remains unclear. Here, we establish isogenic female/male ESCs and show that the female ESCs are more sensitive to camptothecin and have lower gene targeting efficiency than male ESCs, suggesting that homologous recombination (HR) efficiency is reduced in female ESCs. We also generate Xist-inducible female ESCs and show that the lower HR efficiency is restored when X chromosome inactivation is induced. Finally, we assess the X-linked genes with a role in DNA repair and find that Brcc3 is one of the genes involved in a network promoting proper HR. Our findings link the double doses of X-linked genes with lower DNA repair activity, and this may have relevance for common diseases in female patients, such as breast cancer.

中文翻译：

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两条活跃的X染色体减少了雌性胚胎干细胞中的同源重组

在一些原发性乳腺肿瘤中观察到 X 连锁基因的重新激活。在雌性胚胎干细胞 (ESC) 中也观察到两条活跃的 X 染色体，但双剂量的​​ X 连锁基因是否会影响 DNA 修复效率仍不清楚。在这里，我们建立了同基因的雌性/雄性 ESC，并表明雌性 ESC 对喜树碱更敏感，并且比雄性 ESC 具有更低的基因靶向效率，这表明雌性 ESC 中的同源重组 (HR) 效率降低。我们还生成Xist诱导型雌性 ESC，并表明当 X 染色体失活被诱导时，较低的 HR 效率得到恢复。最后，我们评估了在 DNA 修复中起作用的 X 连锁基因，发现Brcc3是参与促进适当 HR 的网络的基因之一。我们的研究结果将双倍剂量的 X 连锁基因与较低的 DNA 修复活性联系起来，这可能与女性患者的常见疾病有关，例如乳腺癌。