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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >MutS inhibits RecA-mediated strand exchange with platinated DNA substrates
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MutS inhibits RecA-mediated strand exchange with platinated DNA substrates

机译：MutS抑制RecA介导的与铂DNA底物的链交换

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摘要

Human cell lines and Escherichia coli dam mutants are sensitive to the cytotoxic action of the anticancer agent, cisplatin. Introduction of mutations disabling DNA mismatch repair into these cell lines renders them resistant to the action of this drug. We used RecA-mediated strand exchange between homologous phiX174 molecules, one that was platinated and the other that was unmodified, to show that strand transfer is decreased in a dose-dependent manner. Transfer was severely decreased at 10 adducts per molecule (5,386 bp) and abolished with 24 adducts. At low levels of adduction, addition of MutS to the reaction further decreases the rate and yield in a dose-dependent manner. MutL addition was without effect even in the presence of MutS. The results suggest that although mismatch repair is beneficial for mutation avoidance, its antirecombination activity on inappropriate substrates can be lethal to the cell.
机译：人细胞系和大肠杆菌dam突变体对抗癌药顺铂的细胞毒性作用敏感。在这些细胞系中引入禁用DNA错配修复的突变，使其对这种药物具有抗性。我们使用RecA介导的同源phiX174分子之间的链交换，一个被镀铂，另一个未被修饰，以显示链转移以剂量依赖性方式减少。转移以每分子10个加合物（5,386 bp）严重降低，并取消了24个加合物。在低加合水平下，将MutS添加到反应中会以剂量依赖性方式进一步降低速率和收率。即使存在MutS，添加MutL也不起作用。结果表明，尽管错配修复有助于避免突变，但其在不适当底物上的抗重组活性可能对细胞具有致命性。

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