| Organisms must protect their DNA if they are to survive and pass their genetic information accurately to their progeny. This is especially true for bacteria and other unicellular organisms, which must constantly deal with stresses in their environments, including nutrient limitation and exposure to DNA-damaging compounds. Cells have evolved methods of detecting specific threats and altering their physiology to respond accordingly. These microbial stress responses are often complex and interconnected, and they often impact the cell’s ability to maintain the integrity of its genetic information.;The work in this dissertation explores relationships among microbial stress responses and maintenance of genomic integrity by focusing on several stress-induced cellular factors in the model bacterium Escherichia coli. Chapter 1 provides an overview of microbial stress responses and their important mediators, and it discusses implications these responses and mediators have for the cell’s ability to protect its DNA. Chapter 2 shares evidence that a stress-induced inorganic molecule, polyphosphate, modulates the activity of DNA polymerase IV, a specialized DNA polymerase that can synthesize damaged template, and it discusses possible mechanisms by which polyphosphate affects the activity of this enzyme. Chapter 3 supplies data indicating that a small, stress-induced protein called YneM and the PhoQ/P two-component system affect phenotypes related to DNA polymerase IV activity. Chapter 4 shows that the AcrAB-TolC multidrug efflux complex and changes in membrane composition mediated by MgrR, a small regulatory RNA, both contribute to the cell’s ability to resist a model DNA-damaging compound called 4-nitroquinoline-1-oxide.;The genetic, molecular biological, and biochemical approaches in this dissertation have identified new relationships among these stress-induced factors and have contributed to a broader understanding of the means by which bacteria maintain the integrity of their genomes in response to environmental stress. |
