The Transcription Factor DksA Prevents Conflicts between DNA Replication and Transcription Machinery

SummaryActively dividing cells perform robust and accurate DNA replication during fluctuating nutrient availability, yet factors that prevent disruption of replication remain largely unknown. Here we report that DksA, a nutrient-responsive transcription factor, ensures replication completion in Escherichia coli by removing transcription roadblocks. In the absence of DksA, replication is rapidly arrested upon amino acid starvation. This arrest requires active transcription and is alleviated by RNA polymerase mutants that compensate for DksA activity. This replication arrest occurs independently of exogenous DNA damage, yet it induces the DNA-damage response and recruits the main recombination protein RecA. This function of DksA is independent of its transcription initiation activity but requires its less-studied transcription elongation activity. Finally, GreA/B elongation factors also prevent replication arrest during nutrient stress. We conclude that transcription elongation factors alleviate fundamental conflicts between replication and transcription, thereby protecting replication fork progression and DNA integrity.

Graphical AbstractFigure optionsDownload high-quality image (339 K)Download as PowerPoint slideHighlights
► E. coli transcription elongation factors resolve replication-transcription conflicts
► DksA functions in transcription elongation in addition to its role in initiation
► Nutritional stress promotes DNA replication-transcription conflicts
► Replication-transcription conflicts contribute to endogenous DNA damage