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Science. 2016 May 20;352(6288):993-6. doi: 10.1126/science.aad6945.

ppGpp couples transcription to DNA repair in E. coli.

Author information

1
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.
2
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
3
Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow 119991, Russia.
4
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.
5
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.

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.

PMID:
27199428
PMCID:
PMC4917784
DOI:
10.1126/science.aad6945
[Indexed for MEDLINE]
Free PMC Article

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