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首页> 外文期刊>Cell cycle >Werner syndrome protein and the MRE11 complex are involved in a common pathway of replication fork recovery.
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Werner syndrome protein and the MRE11 complex are involved in a common pathway of replication fork recovery.

机译：Werner综合征蛋白和MRE11复合物参与复制叉恢复的常见途径。

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Werner syndrome (WS) is an autosomal recessive disease that predisposes individuals to a wide range of cancers. The gene mutated in WS, WRN, encodes a member of the RecQ family of DNA helicases. The precise DNA metabolic processes in which WRN participates remain to be elucidated. However, it has been proposed that WRN might play an important role in the maintenance of genetic stability during DNA replication, possibly cooperating with other proteins. Here, we show that, following DNA replication arrest, WRN associates and colocalizes with the MRE11 complex at PCNA sites. We also provide evidence that both WRN/MRE11 complex association and proper WRN relocalization after HU treatment require a functional MRE11 complex. We demonstrate that mutations altering the functionality of WRN or that of the MRE11 complex result in chromosomal breakage during DNA replication and enhanced cell death following replication arrest. Finally, we show that the DNA breakage in replicating cells and apoptosis observed in WS are not enhanced by concomitant knock down of MRE11 by RNAi, indicating that WRN and MRE11 complex act in a common pathway. These results suggest a functional relationship between WRN and the MRE11 complex in response to replication fork arrest, disclosing a common action of WRN and the MRE11 complex in the pathway(s) preserving genome stability during DNA replication.
机译：Werner综合征（WS）是一种常染色体隐性遗传疾病，易使个体患上多种癌症。 WS中突变的基因WRN编码DNA解旋酶RecQ家族的成员。 WRN参与的确切DNA代谢过程仍有待阐明。然而，已经提出WRN可能在DNA复制过程中在维持遗传稳定性中起重要作用，可能与其他蛋白质协同作用。在这里，我们显示，DNA复制被阻止后，WRN在PCNA站点与MRE11复合体缔合并共定位。我们还提供证据表明，HU治疗后，WRN / MRE11复合体关联和正确的WRN重新定位都需要功能性MRE11复合体。我们证明，改变WRN或MRE11复杂功能的突变导致DNA复制过程中的染色体断裂和复制停止后增强的细胞死亡。最后，我们表明，RNAi对MRE11的伴随敲低并未增强WS中观察到的复制细胞中的DNA断裂和细胞凋亡，这表明WRN和MRE11复合物以共同的途径起作用。这些结果表明，WRN和MRE11复合物之间存在功能性关系，以响应复制叉的阻滞，揭示了WRN和MRE11复合物在DNA复制过程中保持基因组稳定性的途径中的共同作用。

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