高保真DNA复制对于将遗传信息忠实地传递给子细胞至关重要。在基因毒性压力之后，特殊的DNA损伤容忍途径被激活以确保复制叉前进。这些途径包括跨损伤DNA合成、模板切换和复合后再启动。在这篇综述中，我们描述了DNA损伤容忍途径如何影响基因组稳定性、它们与肿瘤发生的关系以及它们对癌症治疗反应的影响。我们讨论了最近的发现，认为单链DNA缺口的积累影响化疗反应，并探讨了越来越多的证据，表明不同的DNA损伤容忍因子，包括跨损伤合成聚合酶、模板切换蛋白和影响单链DNA缺口的酶，是有效的癌症靶点。我们进一步阐述DNA损伤容忍机制的后果如何为发现新的生物标志物提供信息，以优化癌症治疗。© 2022. Springer Nature Limited.

High-fidelity DNA replication is critical for the faithful transmission of genetic information to daughter cells. Following genotoxic stress, specialized DNA damage tolerance pathways are activated to ensure replication fork progression. These pathways include translesion DNA synthesis, template switching and repriming. In this Review, we describe how DNA damage tolerance pathways impact genome stability, their connection with tumorigenesis and their effects on cancer therapy response. We discuss recent findings that single-strand DNA gap accumulation impacts chemoresponse and explore a growing body of evidence that suggests that different DNA damage tolerance factors, including translesion synthesis polymerases, template switching proteins and enzymes affecting single-stranded DNA gaps, represent useful cancer targets. We further outline how the consequences of DNA damage tolerance mechanisms could inform the discovery of new biomarkers to refine cancer therapies.© 2022. Springer Nature Limited.