Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ, UK.
Mol Cell. 2010 Feb 26;37(4):492-502. doi: 10.1016/j.molcel.2010.01.021.
Faithful DNA replication is essential to all life. Hydroxyurea (HU) depletes the cells of dNTPs, which initially results in stalled replication forks that, after prolonged treatment, collapse into DSBs. Here, we report that stalled replication forks are efficiently restarted in a RAD51-dependent process that does not trigger homologous recombination (HR). The XRCC3 protein, which is required for RAD51 foci formation, is also required for replication restart of HU-stalled forks, suggesting that RAD51-mediated strand invasion supports fork restart. In contrast, replication forks collapsed by prolonged replication blocks do not restart, and global replication is rescued by new origin firing. We find that RAD51-dependent HR is triggered for repair of collapsed replication forks, without apparent restart. In conclusion, our data suggest that restart of stalled replication forks and HR repair of collapsed replication forks require two distinct RAD51-mediated pathways.
忠实的 DNA 复制对所有生命都是必不可少的。羟基脲（HU）耗尽细胞中的 dNTP，最初导致复制叉停滞，经过长时间的治疗后，复制叉崩溃成 DSB。在这里，我们报告说，停滞的复制叉通过 RAD51 依赖性过程有效地重新启动，该过程不会触发同源重组（HR）。XRCC3 蛋白是 RAD51 焦点形成所必需的，对于 HU 停滞的叉子的复制重新启动也是必需的，这表明 RAD51 介导的链入侵支持叉子重新启动。相比之下，由长时间复制块引起的复制叉崩溃不会重新启动，并且通过新的起始点火来挽救全局复制。我们发现，对于崩溃的复制叉的修复，会触发依赖 RAD51 的 HR，而没有明显的重新启动。总之，我们的数据表明，停滞的复制叉的重新启动和崩溃的复制叉的 HR 修复需要两种不同的 RAD51 介导的途径。
