Gross chromosomal rearrangements and elevated recombination at an inducible site-specific replication fork barrier
Gross chromosomal rearrangements and elevated recombination at an inducible site-specific replication fork barrier
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DOI：
10.1016/j.cell.2005.03.022
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发表时间：
2005-06-03
期刊：
影响因子：
64.5
通讯作者：
Carr, AM
中科院分区：
文献类型：
--
作者：
Lambert, S;Watson, A;Carr, AM
与异常重组相关的基因组重排与癌症和人类遗传疾病有关。这种重组间接地与复制叉停滞有关。使用裂变酵母，我们已经开发出一种遗传系统，以阻止复制叉在非组蛋白/DNA复合物位于一个特定的常染色质位点。我们证明，停滞的复制叉导致升高的染色体内和异位重组，促进位点特异性的总染色体重排。我们表明，重组是必要的，以促进细胞活力时，叉失速，重组蛋白与叉失速的网站，重组参与有害的位点特异性染色体重排。因此，重组是一把“双刃剑”，当复制体以遗传稳定性为代价进行分解时，可以防止细胞死亡。
Genomic rearrangements linked to aberrant recombination are associated with cancer and human genetic diseases. Such recombination has indirectly been linked to replication fork stalling. Using fission yeast, we have developed a genetic system to block replication forks at nonhistone/DNA complexes located at a specific euchromatic site. We demonstrate that stalled replication forks lead to elevated intrachromosomal and ectopic recombination promoting site-specific gross chromosomal rearrangements. We show that recombination is required to promote cell viability when forks are stalled, that recombination proteins associate with sites of fork stalling, and that recombination participates in deleterious site-specific chromosomal rearrangements. Thus, recombination is a "double-edged sword," preventing cell death when the replisome disassembles at the expense of genetic stability.