A role for the umuDC gene products of Escherichia coli in increasing resistance to DNA damage in stationary phase by inhibiting the transition to exponential growth.
The umuDC gene products, whose expression is induced by DNA-damaging treatments, have been extensively characterized for their role in SOS mutagenesis. We have recently presented evidence that supports a role for the umuDC gene products in the regulation of growth after DNA damage in exponentially growing cells, analogous to a prokaryotic DNA damage checkpoint. Our further characterization of the growth inhibition at 30 degrees C associated with constitutive expression of the umuDC gene products from a multicopy plasmid has shown that the umuDC gene products specifically inhibit the transition from stationary phase to exponential growth at the restrictive temperature of 30 degrees C and that this is correlated with a rapid inhibition of DNA synthesis. These observations led to the finding that physiologically relevant levels of the umuDC gene products, expressed from a single, SOS-regulated chromosomal copy of the operon, modulate the transition to rapid growth in E. coli cells that have experienced DNA damage while in stationary phase. This activity of the umuDC gene products is correlated with an increase in survival after UV irradiation. In a distinction from SOS mutagenesis, uncleaved UmuD together with UmuC is responsible for this activity. The umuDC-dependent increase in resistance in UV-irradiated stationary-phase cells appears to involve, at least in part, counteracting a Fis-dependent activity and thereby regulating the transition to rapid growth in cells that have experienced DNA damage. Thus, the umuDC gene products appear to increase DNA damage tolerance at least partially by regulating growth after DNA damage in both exponentially growing and stationary-phase cells.
Murli
S
S
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Opperman
T
T
Smith
B T
BT
Walker
G C
GC
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication / Q000235:genetics / Q000528:radiation effects; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000528:radiation effects*; D029968:Escherichia coli Proteins; D035021:Factor For Inversion Stimulation Protein; D015964:Gene Expression Regulation, Bacterial; D034982:Integration Host Factors; D013014:SOS Response, Genetics; D013997:Time Factors; D014466:Ultraviolet Rays
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D035021:Factor For Inversion Stimulation Protein; D034982:Integration Host Factors; C440502:integration host factor, E coli; C078202:UmuC protein, E coli; D004259:DNA-Directed DNA Polymerase; C055218:UmuD protein, E coli