title: The transcription factor DksA prevents conflicts between DNA replication and transcription machinery.
abstract: Actively 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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Ashley K
authors.initials: AK
authors.lastname: Tehranchi
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Blankschien
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Halliday
authors.forename: Anjana
authors.initials: A
authors.lastname: Srivatsan
authors.forename: Jia
authors.initials: J
authors.lastname: Peng
authors.forename: Christophe
authors.initials: C
authors.lastname: Herman
authors.forename: Jue D
authors.initials: JD
authors.lastname: Wang
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006158:Guanosine Pentaphosphate / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000596:Amino Acids; D029968:Escherichia coli Proteins; C090751:dksA protein, E coli; D006158:Guanosine Pentaphosphate