Mus81 is essential for sister chromatid recombination at broken replication forks
Mus81 is essential for sister chromatid recombination at broken replication forks
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DOI：
10.1038/emboj.2008.65
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发表时间：
2008-05-07
期刊：
影响因子：
11.4
通讯作者：
Arcangioli, Benoit
中科院分区：
文献类型：
--
作者：
Roseaulin, Laura;Yamada, Yoshiki;Arcangioli, Benoit
重复对于恢复停滞/崩溃的复制叉是必不可少的，因此对于维持基因组稳定性是必不可少的。当复制叉与未修复的单链断裂发生碰撞并将其转化为单端双链断裂时，情况变得至关重要。我们表明，在分裂酵母，一个独特的破碎的复制叉需要同源重组（HR）酶的细胞活力。两种结构特异性异二聚体核酸内切酶参与两种不同的拆分途径。当姐妹染色单体用于修复时，Mus 81/Eme 1是必需的;相反，当异位序列用于修复时，Swi 9/Swi 10是必需的。因此，这两种HR解析模式的利用主要依赖于各种真核生物基因组中存在的独特序列和重复序列的比率。我们还提供了姐妹重组中间体的分子证据。这些研究结果表明，Mus 81/Eme 1是专用的内切核酸酶，解决了姐妹染色单体重组中间体在修复断裂的复制叉。
Recombination is essential for the recovery of stalled/collapsed replication forks and therefore for the maintenance of genomic stability. The situation becomes critical when the replication fork collides with an unrepaired single-strand break and converts it into a one-ended double-strand break. We show in fission yeast that a unique broken replication fork requires the homologous recombination (HR) enzymes for cell viability. Two structure-specific heterodimeric endonucleases participate in two different resolution pathways. Mus81/Eme1 is essential when the sister chromatid is used for repair; conversely, Swi9/Swi10 is essential when an ectopic sequence is used for repair. Consequently, the utilization of these two HR modes of resolution mainly relies on the ratio of unique and repeated sequences present in various eukaryotic genomes. We also provide molecular evidence for sister recombination intermediates. These findings demonstrate that Mus81/Eme1 is the dedicated endonuclease that resolves sister chromatid recombination intermediates during the repair of broken replication forks.