Complete and accurate DNA replication requires the progression of replication forks through DNA damage, actively transcribed regions, structured DNA and compact chromatin. Recent studies have revealed a remarkable plasticity of the replication process in dealing with these obstacles, which includes modulation of replication origin firing, of the architecture of replication forks, and of the functional organization of the replication machinery in response to replication stress. However, these specialized mechanisms also expose cells to potentially dangerous transactions while replicating DNA. In this Review, we discuss how replication forks are actively stalled, remodelled, processed, protected and restarted in response to specific types of stress. We also discuss adaptations of the replication machinery and the role of chromatin modifications during these transactions. Finally, we discuss interesting recent data on the relevance of replication fork plasticity to human health, covering its role in tumorigenesis, its crosstalk with innate immunity responses and its potential as an effective cancer therapy target.

完整而准确的DNA复制需要通过DNA损伤，活跃转录的区域，结构化DNA和紧密染色质来实现复制叉的发展。最近的研究表明，复制过程在处理这些障碍方面具有显着的可塑性，这些障碍包括调制复制起点触发，复制叉的体系结构以及响应复制压力的复制机器的功能组织。但是，这些专门的机制在复制DNA时也会使细胞面临潜在的危险交易。在这篇评论中，我们讨论了如何响应特定的压力类型积极地停止，重构，处理，保护和重新启动复制叉。我们还将讨论在这些交易过程中复制机制的适应以及染色质修饰的作用。最后，我们讨论了有关复制叉可塑性与人类健康相关性的有趣最新数据，包括其在肿瘤发生中的作用，与先天免疫反应的串扰以及作为有效癌症治疗靶标的潜力。