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首页> 外文期刊>Molecular and Cellular Biology >Different Roles for Nonhomologous End Joining and Homologous Recombination following Replication Arrest in Mammalian Cells
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Different Roles for Nonhomologous End Joining and Homologous Recombination following Replication Arrest in Mammalian Cells

机译：在哺乳动物细胞中复制逮捕后非同源末端连接和同源重组的不同作用。

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Homologous recombination (HR) and nonhomologous end joining (NHEJ) play overlapping roles in repair of DNA double-strand breaks (DSBs) generated during the S phase of the cell cycle. Here, we characterized the involvement of HR and NHEJ in the rescue of DNA replication forks arrested or slowed by treatment of hamster cells with hydroxyurea or thymidine. We show that the arrest of replication with hydroxyurea generates DNA fragmentation as a consequence of the formation of DSBs at newly replicated DNA. Both HR and NHEJ protected cells from the lethal effects of hydroxyurea, and this agent also increased the frequency of recombination mediated by both homologous and nonhomologous exchanges. Thymidine induced a less stringent arrest of replication and did not generate detectable DSBs. HR alone rescued cells from the lethal effects of thymidine. Furthermore, thymidine increased the frequency of DNA exchange mediated solely by HR in the absence of detectable DSBs. Our data suggest that both NHEJ and HR are involved in repair of arrested replication forks that include a DSB, while HR alone is required for the repair of slowed replication forks in the absence of detectable DSBs.
机译：同源重组（HR）和非同源末端连接（NHEJ）在细胞周期S期产生的DNA双链断裂（DSB）修复中起重叠作用。在这里，我们表征了HR和NHEJ参与通过用羟基脲或胸苷处理仓鼠细胞而停滞或减慢的DNA复制叉的拯救。我们表明，与羟基脲复制的逮捕由于新复制的DNA形成DSBs而产生DNA断裂。 HR和NHEJ均可保护细胞免受羟基脲的致死作用，并且该试剂还增加了同源和非同源交换介导的重组频率。胸腺嘧啶核苷导致复制的抑制作用较不严格，并且未产生可检测的DSB。单独的HR可以使细胞免受胸腺嘧啶的致死作用。此外，在没有可检测的DSB的情况下，胸苷增加了仅由HR介导的DNA交换的频率。我们的数据表明，NHEJ和HR都参与了包括DSB在内的被捕复制叉的修复，而在没有可检测DSB的情况下，慢速复制叉的修复仅需HR。

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