Cell fitness and survival upon exposure to DNA damage depends on the repair of DNA lesions. Interestingly, cellular identity does affect and finetunes such response, although the molecular basis of such differences between tissues and cell types is not well understood. Thus, a possibility is that DNA repair itself is controlled by the mechanisms that govern cell identity. Here we show that the KLF4, involved in cellular homeostasis, proliferation, cell reprogramming and cancer development, directly regulates resection and homologous recombination proficiency. Indeed, resection efficiency follows KLF4 protein levels, i.e. decreases upon KLF4 downregulation and increases when is overexpressed. Moreover, KLF4 role in resection requires its methylation by the methyl-transferase PRMT5. Thus, PRMT5 depletion not only mimics KLF4 downregulation, but also showed an epistatic genetic relationship. Our data support a model in which the methylation of KLF4 by PRMT5 is a priming event required to license DNA resection and homologous recombination.

暴露于DNA损伤下的细胞适应性和存活率取决于DNA损伤的修复。有趣的是，尽管对组织和细胞类型之间这种差异的分子基础尚不十分了解，但细胞身份确实会影响并微调这种反应。因此，一种可能性是DNA修复本身受控制细胞身份的机制控制。在这里，我们显示参与细胞稳态，增殖，细胞重编程和癌症发展的KLF4直接调节切除和同源重组水平。实际上，切除效率遵循KLF4蛋白水平，即在KLF4下调后降低，而在过表达时提高。此外，KLF4在切除中的作用要求其被甲基转移酶PRMT5甲基化。因此，PRMT5消耗不仅模拟了KLF4的下调，而且还表现出上位的遗传关​​系。我们的数据支持一个模型，其中PRMT5对KLF4的甲基化是许可DNA切除和同源重组所需的引发事件。