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Homologous recombination and Mus81 promote replication completion in response to replication fork blockage.
EMBO Reports ( IF 7.7 ) Pub Date : 2020-05-17 , DOI: 10.15252/embr.201949367
Benjamin Pardo 1, 2 , María Moriel-Carretero 1, 2 , Thibaud Vicat 1 , Andrés Aguilera 2 , Philippe Pasero 1
Affiliation  

Impediments to DNA replication threaten genome stability. The homologous recombination (HR ) pathway has been involved in the restart of blocked replication forks. Here, we used a method to increase yeast cell permeability in order to study at the molecular level the fate of replication forks blocked by DNA topoisomerase I poisoning by camptothecin (CPT ). Our results indicate that Rad52 and Rad51 HR factors are required to complete DNA replication in response to CPT . Recombination events occurring during S phase do not generally lead to the restart of DNA synthesis but rather protect blocked forks until they merge with convergent forks. This fusion generates structures requiring their resolution by the Mus81 endonuclease in G2/M. At the global genome level, the multiplicity of replication origins in eukaryotic genomes and the fork protection mechanism provided by HR appear therefore to be essential to complete DNA replication in response to fork blockage.

中文翻译:

同源重组和 Mus81 促进复制完成以响应复制叉阻塞。

DNA复制的障碍威胁着基因组的稳定性。同源重组 (HR) 途径参与了受阻复制叉的重启。在这里,我们使用了一种增加酵母细胞通透性的方法,以便在分子水平上研究被喜树碱 (CPT) 中毒的 DNA 拓扑异构酶 I 阻断的复制叉的命运。我们的结果表明 Rad52 和 Rad51 HR 因子是响应 CPT 完成 DNA 复制所必需的。在 S 期发生的重组事件通常不会导致 DNA 合成的重新开始,而是保护阻塞的叉,直到它们与会聚叉合并。这种融合产生的结构需要被 G 2中的 Mus81 核酸内切酶解析/米。因此,在全球基因组水平上,真核基因组中复制起点的多样性和 HR 提供的叉保护机制似乎对于完成 DNA 复制以响应叉阻塞是必不可少的。
更新日期:2020-07-03
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