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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.
Copyright (c) 2010 Elsevier Inc. All rights reserved.