Modulation of RNA polymerase by (p)ppGpp reveals a RecG-dependent mechanism for replication fork progression

We have discovered a correlation between the ability of Escherichia coli ce lls to survive damage to DNA and their ability to modulate RNA polymerase v ia the stringent response regulators, (p)ppGpp. Elevation of (p)ppGpp, or c ertain mutations in the beta subunit of RNA polymerase, dramatically improv e survival of UV-irradiated strains lacking the RuvABC Holliday junction re solvase. Increased survival depends on excision and recombination proteins and relies on the ability of RecG helicase to form Holliday junctions from replication forks stalled at lesions in the DNA and of PriA to initiate rep lication restart. The role of RecG provides novel insights into the interpl ay between transcription, replication, and recombination, and suggests a ge neral model in which recombination underpins genome duplication in the face of frequent obstacles to replication fork progression.