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Dose‐dependent reduction of replication elongation rate by (p)pp G pp in E scherichia coli and B acillus subtilis
Author(s) -
DeNapoli Jessica,
Tehranchi Ashley K.,
Wang Jue D.
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12172
Subject(s) - stringent response , biology , bacillus subtilis , elongation , dna replication , escherichia coli , bacteria , microbiology and biotechnology , mutant , biochemistry , dna , genetics , gene , materials science , ultimate tensile strength , metallurgy
Summary DNA replication is regulated in response to environmental constraints such as nutrient availability. While much is known about regulation of replication during initiation, little is known about regulation of replication during elongation. In the bacterium B acillus subtilis , replication elongation is paused upon sudden amino acid starvation by the starvation‐inducible nucleotide (p)pp G pp. However, in many bacteria including E scherichia coli , replication elongation is thought to be unregulated by nutritional availability. Here we reveal that the replication elongation rate in E . coli is modestly but significantly reduced upon strong amino acid starvation. This reduction requires (p)pp G pp and is exacerbated in a gppA mutant with increased ppp G pp levels. Importantly, high levels of (p)pp G pp, independent of amino acid starvation, are sufficient to inhibit replication elongation even in the absence of transcription. Finally, in both E . coli and B . subtilis , (p)pp G pp inhibits replication elongation in a dose‐dependent manner rather than via a switch‐like mechanism, although this inhibition is much stronger in B . subtilis . This supports a model where replication elongation rates are regulated by (p)pp G pp to allow rapid and tunable response to multiple abrupt stresses in evolutionarily diverse bacteria.