Fun30 is an ATP‐dependent chromatin remodeler in budding yeast that is involved in cellular processes important for maintaining genomic stability such as gene silencing and DNA damage repair. Cells lacking Fun30 are moderately sensitive to the topoisomerase inhibitor camptothecin and exhibit a delay in cell cycle progression in the presence of camptothecin. Here, we show that Fun30 is required to cope with torsional stress in the absence of Top1. Moreover, we show through genetic studies that Fun30 acts in a parallel pathway to Mus81 endonuclease but is epistatic to Tdp1 phosphodiesterase and Rad1 endonuclease in the repair of camptothecin‐induced DNA damage. More importantly, we show that DNA damage sensitivity of Fun30 deficient cells is enhanced in the absence of RNase H enzymes that remove RNA:DNA hybrids. We believe that chromatin remodeling by Fun30 may be important in dealing with torsional stress and camptothecin‐induced DNA damage.

中文翻译：

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Fun30 染色质重塑剂有助于应对扭转应力和喜树碱诱导的 DNA 损伤

Fun30 是出芽酵母中 ATP 依赖性染色质重塑剂，它参与对维持基因组稳定性很重要的细胞过程，如基因沉默和 DNA 损伤修复。缺乏 Fun30 的细胞对拓扑异构酶抑制剂喜树碱中度敏感，并且在喜树碱存在下会延迟细胞周期进程。在这里，我们展示了在没有 Top1 的情况下需要 Fun30 来应对扭转应力。此外，我们通过遗传研究表明，Fun30 在与 Mus81 核酸内切酶平行的途径中起作用，但在喜树碱诱导的 DNA 损伤修复中对 Tdp1 磷酸二酯酶和 Rad1 核酸内切酶具有上位性。更重要的是，我们表明在缺乏去除 RNA:DNA 杂交体的 RNase H 酶的情况下，Fun30 缺陷细胞的 DNA 损伤敏感性得到增强。