A gatekeeping function of the replicative polymerase controls pathway choice in the resolution of lesion-stalled replisomes

Abstract

Significance DNA replication is the high-fidelity process by which cells duplicate their chromosomes prior to cell division. Cellular DNA is constantly damaged, and the resulting DNA lesions can block replication, leading to genome instability and cell death. Cells use multiple pathways to resolve stalled replication. Understanding resolution pathway choice is important because some of these pathways are more likely to introduce mutations than others. In bacterial cells, replication stresses, including antibiotic treatment, lead to mutagenesis, which may contribute to the emergence of antibiotic resistance. In this study, we describe a molecular interaction within the Escherichia coli replication machinery that plays a crucial role in resolution pathway choice, thereby influencing whether lesion-stalled replication is resolved in an error-prone or error-free manner.