DNA repair by homologous recombination (HR) is essential for genomic integrity, tumor suppression, and the formation of gametes. HR uses DNA synthesis to repair lesions such as DNA double-strand breaks and stalled DNA replication forks, but despite having a good understanding of the steps leading to homology search and strand invasion, we know much less of the mechanisms that establish recombination-associated DNA polymerization. Here, we report that C17orf53/HROB is an OB-fold-containing factor involved in HR that acts by recruiting the MCM8-MCM9 helicase to sites of DNA damage to promote DNA synthesis. Mice with targeted mutations in Hrob are infertile due to depletion of germ cells and display phenotypes consistent with a prophase I meiotic arrest. The HROB-MCM8-MCM9 pathway acts redundantly with the HELQ helicase, and cells lacking both HROB and HELQ have severely impaired HR, suggesting that they underpin two major routes for the completion of HR downstream from RAD51. The function of HROB in HR is reminiscent of that of gp59, which acts as the replicative helicase loader during bacteriophage T4 recombination-dependent DNA replication. We therefore propose that the loading of MCM8-MCM9 by HROB may similarly be a key step in the establishment of mammalian recombination-associated DNA synthesis.

中文翻译：

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通过HROB-MCM8-MCM9途径控制同源重组。

通过同源重组（HR）进行的DNA修复对于基因组完整性，肿瘤抑制和配子形成至关重要。HR使用DNA合成来修复诸如DNA双链断裂和停滞的DNA复制叉之类的损伤，但是尽管对导致同源性搜索和链入侵的步骤有了很好的了解，但我们对建立与重组相关的DNA的机制了解较少聚合。在这里，我们报道C17orf53 / HROB是参与HR的含有OB折叠的因子，该因子通过将MCM8-MCM9解旋酶募集到DNA损伤部位来促进DNA合成。由于生殖细胞的耗竭，具有Hrob靶向突变的小鼠是不育的，并且表现出与前期减数分裂停滞相符的表型。HROB-MCM8-MCM9途径与HELQ解旋酶重复作用，缺乏HROB和HELQ的细胞严重损害了HR，这表明它们是RAD51下游完成HR的两条主要途径的基础。HROB在HR中的功能让人联想到gp59，后者在噬菌体T4重组依赖的DNA复制过程中充当复制解旋酶装载剂。因此，我们建议由HROB加载MCM8-MCM9可能是建立哺乳动物重组相关DNA合成中的关键步骤。