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首页> 外文期刊>Molecular and Cellular Biology >Fission Yeast Cut8 Is Required for the Repair of DNA Double-Strand Breaks, Ribosomal DNA Maintenance, and Cell Survival in the Absence of Rqh1 Helicase
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Fission Yeast Cut8 Is Required for the Repair of DNA Double-Strand Breaks, Ribosomal DNA Maintenance, and Cell Survival in the Absence of Rqh1 Helicase

机译：裂变酵母Cut8是修复Rqh1解旋酶时DNA双链断裂，核糖体DNA维持和细胞存活所必需的。

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Schizosaccharomyces pombe Rqh1 is a member of the RecQ DNA helicase family. Members of this protein family are mutated in cancer predisposition diseases, causing Bloom's, Werner, and Rothmund-Thomson syndromes. Rqh1 forms a complex with topoisomerase III and is proposed to process or disrupt aberrant recombination structures that arise during S phase to allow proper chromosome segregation during mitosis. Intriguingly, in the absence of Rqh1, processing of these structures appears to be dependent on Rad3 (human ATR) in a manner that is distinct from its role in checkpoint control. Here, we show that rad3 rqh1 mutants are normally committed to a lethal pathway of DNA repair requiring homologous recombination, but blocking this pathway by Rhp51 inactivation restores viability. Remarkably, viability is also restored by overexpression of Cut8, a nuclear envelope protein involved in tethering and proper function of the proteasome. In keeping with a recently described function of the proteasome in the repair of DNA double-strand breaks, we found that Cut8 is also required for DNA double-strand break repair and is essential for proper chromosome segregation in the absence of Rqh1, suggesting that these proteins might function in a common pathway in homologous recombination repair to ensure accurate nuclear division in S. pombe.
机译：粟酒裂殖酵母 Rqh1是RecQ DNA解旋酶家族的成员。该蛋白家族的成员在癌症易感性疾病中发生突变，从而引起Bloom's，Werner和Rothmund-Thomson综合征。 Rqh1与拓扑异构酶III形成复合物，被提议用于处理或破坏S期出现的异常重组结构，从而在有丝分裂期间允许正确的染色体分离。有趣的是，在不存在Rqh1的情况下，这些结构的处理似乎依赖于Rad3（人类ATR），其方式不同于其在检查点控制中的作用。在这里，我们显示 rad3 rqh1 突变体通常致力于需要同源重组的致命DNA修复途径，但通过Rhp51失活阻断该途径可恢复活力。值得注意的是，过表达Cut8（一种与蛋白酶体的系链和适当功能有关的核被膜蛋白）也可以恢复活力。为了与蛋白酶体在DNA双链断裂修复中的最新功能保持一致，我们发现Cut8也是DNA双链断裂修复所必需的，并且在缺少Rqh1的情况下对于正确的染色体分离也是必不可少的，这表明这些蛋白可能在同源重组修复的共同途径中起作用，以确保 S中的精确核分裂。蓬贝。

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