DNA damage tolerance (DDT) is crucial for genome integrity maintenance. DDT is mainly carried out by template switch recombination, an error-free mode of overcoming DNA lesions, or translesion DNA synthesis, which is error-prone. Here, we investigated the role of Mgs1/WRNIP1 in modulating DDT. Using budding yeast, we found that elimination of Mgs1 in cells lacking Rad5, an essential protein for DDT, activates an alternative mode of DNA damage bypass, driven by recombination, which allows chromosome replication and cell viability under stress conditions that block DNA replication forks. This salvage pathway is RAD52 and RAD59 dependent, requires the DNA polymerase δ and PCNA modification at K164, and is enabled by Esc2 and the PCNA unloader Elg1, being inhibited when Mgs1 is present. We propose that Mgs1 is necessary to prevent a potentially toxic recombination salvage pathway at sites of perturbed replication, which, in turn, favors Rad5-dependent template switching, thus helping to preserve genome stability.

中文翻译：

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Mgs1 / WRNIP1 ATPase是必需的，以防止在损坏的复制叉处发生重组挽救途径。

DNA损伤耐受性（DDT）对于维持基因组完整性至关重要。DDT主要通过模板开关重组，克服DNA损伤的无错误模式或易发生错误的跨病变DNA合成来进行。在这里，我们调查了Mgs1 / WRNIP1在调节DDT中的作用。使用发芽的酵母，我们发现在缺少Rad5（DDT的必需蛋白）的细胞中消除Mgs1激活了由重组驱动的DNA损伤旁路的另一种模式，这可以在阻止DNA复制叉的压力条件下实现染色体复制和细胞活力。该挽救途径是RAD52和RAD59依赖的，需要在K164处进行DNA聚合酶δ和PCNA修饰，并由Esc2和PCNA卸载子Elg1启用，当存在Mgs1时被抑制。