Most tumors lack the G1/S phase checkpoint and are insensitive to antigrowth signals. Loss of G1/S control can severely perturb DNA replication as revealed by slow replication fork progression and frequent replication fork stalling. Cancer cells may thus rely on specific pathways that mitigate the deleterious consequences of replication stress. To identify vulnerabilities of cells suffering from replication stress, we performed an shRNA-based genetic screen. We report that the RECQL helicase is specifically essential in replication stress conditions and protects stalled replication forks against MRE11-dependent double strand break (DSB) formation. In line with these findings, knockdown of RECQL in different cancer cells increased the level of DNA DSBs. Thus, RECQL plays a critical role in sustaining DNA synthesis under conditions of replication stress and as such may represent a target for cancer therapy.

中文翻译：

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RECQL解旋酶可防止复制压力期间复制叉崩溃。

大多数肿瘤缺乏G1 / S期检查点，并且对抗生长信号不敏感。G1 / S控制的丧失会严重干扰DNA复制，如复制叉进展缓慢和复制叉频繁停滞所揭示。因此，癌细胞可能依赖减轻复制压力的有害后果的特定途径。为了确定遭受复制压力的细胞的脆弱性，我们进行了基于shRNA的遗传筛选。我们报告说，RECQL解旋酶在复制压力条件下特别重要，可以保护停滞的复制叉免受MRE11依赖的双链断裂（DSB）的形成。与这些发现一致，不同癌细胞中RECQL的敲低增加了DNA DSB的水平。从而，