Leveraging the replication stress response to optimize cancer therapy

Emily Cybulla, Alessandro Vindigni

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations


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.

Original languageEnglish
Pages (from-to)6-24
Number of pages19
JournalNature Reviews Cancer
Issue number1
StatePublished - Jan 2023


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