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ppGpp couples transcription to DNA repair in E. coli

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Science  20 May 2016:
Vol. 352, Issue 6288, pp. 993-996
DOI: 10.1126/science.aad6945

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A starvation survival signal fights DNA damage

The alarmone guanosine-3′,5′-(bis)pyrophosphate (ppGpp) shuts down transcription in bacteria that are starving. This “stringent response” helps them conserve energy and survive adverse conditions. Kamarthapu et al. show that ppGpp is also essential for DNA repair. ppGpp couples transcription elongation to the nucleotide excision repair pathway. ppGpp helps backtrack the RNA polymerase away from the DNA damage to facilitate repair. Through inhibiting DNA replication, it also avoids dangerous collisions between the replication fork and backtracked RNA polymerase.

Science, this issue p. 993

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.

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