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

摘要

Actively dividing cells perform robust and accurate DNA replication during fluctuating nutrient avail-ability, yet factors that prevent disruption of replica-tion 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 tran-scription and is alleviated by RNA polymerase mutants that compensate for DksA activity. This replication arrest occurs independently of exoge-nous 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.