A homologous recombination defect affects replication-fork progression in mammalian cells
A homologous recombination defect affects replication-fork progression in mammalian cells
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DOI：
10.1242/jcs.010330
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发表时间：
2008-01-15
影响因子：
4
通讯作者：
Lopez, Bernard S.
中科院分区：
文献类型：
--
作者：
Daboussi, Fayza;Courbet, Sylvain;Lopez, Bernard S.
忠实的基因组传递需要一个协调DNA复制到DNA修复和重组的途径网络。在这里，我们使用分子梳理来测量同源重组（HR）对DNA复制叉速度的影响。我们使用了三个仓鼠细胞系缺陷的HR要么过表达的一个RAD51显性阴性的形式，或由一个缺陷的RAD51 paradoxin XRCC 2或乳腺癌抑制BRCA 2。无论HR改变的类型或程度如何，所有三种细胞系都表现出类似的复制叉进展速率降低，与复制叉密度增加相关。重要的是，这种表型在Xrcc2和Brca2突变体的互补衍生物中完全逆转。这些数据揭示了HR的新作用，不同于停滞的复制叉的重新激活，其可能在基因组稳定性中起重要作用，从而在肿瘤保护中起重要作用。
Faithful genome transmission requires a network of pathways coordinating DNA replication to DNA repair and recombination. Here, we used molecular combing to measure the impact of homologous recombination (HR) on the velocity of DNA replication forks. We used three hamster cell lines defective in HR either by overexpression of a RAD51 dominant-negative form, or by a defect in the RAD51 paralogue XRCC2 or the breast tumor suppressor BRCA2. Irrespectively of the type or extent of HR alteration, all three cell lines exhibited a similar reduction in the rate of replication-fork progression, associated with an increase in the density of replication forks. Importantly, this phenotype was completely reversed in complemented derivatives of Xrcc2 and Brca2 mutants. These data reveal a novel role for HR, different from the reactivation of stalled replication forks, which may play an important role in genome stability and thus in tumor protection.