The repair of DNA double-strand breaks occurs through nonhomologous end joining or homologous recombination in vertebrate cells-a choice that is thought to be decided by a competition between DNA-dependent protein kinase (DNA-PK) and the Mre11/Rad50/Nbs1 (MRN) complex but is not well understood. Using ensemble biochemistry and single-molecule approaches, here, we show that the MRN complex is dependent on DNA-PK and phosphorylated CtIP to perform efficient processing and resection of DNA ends in physiological conditions, thus eliminating the competition model. Endonucleolytic removal of DNA-PK-bound DNA ends is also observed at double-strand break sites in human cells. The involvement of DNA-PK in MRN-mediated end processing promotes an efficient and sequential transition from nonhomologous end joining to homologous recombination by facilitating DNA-PK removal.

中文翻译：

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DNA依赖性蛋白激酶通过MRN和CtIP促进DNA末端加工。

DNA双链断裂的修复通过脊椎动物细胞中的非同源末端连接或同源重组而发生，这一选择被认为是由DNA依赖性蛋白激酶（DNA-PK）与Mre11 / Rad50 / Nbs1（ MRN），但尚未被很好地理解。在这里，使用整体生物化学和单分子方法，我们表明MRN复合物依赖于DNA-PK和磷酸化的CtIP在生理条件下进行有效的DNA末端切割和切除，从而消除了竞争模型。在人细胞中的双链断裂位点也观察到了DNA-PK结合的DNA末端的核酸内切去除。