title: ppGpp couples transcription to DNA repair in E. coli.
abstract: The small molecule alarmone (p)ppGpp mediates bacterial adaptation to nutrient deprivation by altering the initiation properties of RNA polymerase (RNAP). ppGpp is generated in Escherichia coli by two related enzymes, RelA and SpoT. We show that ppGpp is robustly, but transiently, induced in response to DNA damage and is required for efficient nucleotide excision DNA repair (NER). This explains why relA-spoT-deficient cells are sensitive to diverse genotoxic agents and ultraviolet radiation, whereas ppGpp induction renders them more resistant to such challenges. The mechanism of DNA protection by ppGpp involves promotion of UvrD-mediated RNAP backtracking. By rendering RNAP backtracking-prone, ppGpp couples transcription to DNA repair and prompts transitions between repair and recovery states.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Venu
authors.initials: V
authors.lastname: Kamarthapu
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Epshtein
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Benjamin
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow 119991, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Proshkin
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow 119991, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mironov
authors.affiliation: Division of Developmental Biology, Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Cashel
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA. evgeny.nudler@nyumc.org.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Nudler
mesh_terms: D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism; D004260:DNA Repair; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000378:metabolism; D006159:Guanosine Tetraphosphate / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D029968:Escherichia coli Proteins; D006159:Guanosine Tetraphosphate; D012321:DNA-Directed RNA Polymerases; C506746:UvrD protein, E coli; D004265:DNA Helicases