Faculty & Research
- Contact Information
- Contact Patricia Foster by plfoster [at] indiana [dot] edu
- By telephone: 812-855-4084/5-4054(lab)
- JH 447E / JH 447A(lab)
- Research Areas
- Chromatin, Chromosomes, and Genome Integrity
- Genomics and Bioinformatics
- Microbial Cell Biology and Environmental Responses
Ph.D., Cambridge University, UK, 1978
Postdoctoral Fellow: MIT, 1978-80; Harvard Medical School, 1980-84
Fellow, American Academy of Microbiology
Fellow, American Association for the Advancement of Science
In the Spotlight, Encyclopedia of Life Sciences, 2011
Mutations are heritable changes in an organism’s genome. On an evolutionary scale, mutations are the source of variation upon which natural selection works. On a human scale, mutations give rise to birth defects, genetic diseases, and cancer. Using the bacterium Escherichia coli as a model system, my laboratory employs genetic and molecular techniques to investigate the molecular mechanisms by which mutations arise spontaneously and as a result of DNA damage.
Spontaneous mutation - Spontaneous mutations arise not only during cell growth, but also in nondividing cells that are exposed to stress, a phenomenon called adaptive mutation. We found that a novel type of recombination-dependent mutational process gives rise to these adaptive mutations. We are investigating the molecular mechanism of recombination-dependent mutation, and are determining its general importance. Other examples of adaptive mutation that are not recombination-dependent are being investigated. Recent evidence suggests that during stress a subpopulation of cells enters into a transient state of hypermutation, and that these cells give rise to both adaptive and nonadaptive mutations. We are investigating the genetic bases of this transient mutator state. Other interests include: (1) the role of mismatch repair in adaptive mutation; (2) the importance of the conjugal plasmids in bacterial evolution; (3) the influence of chromosome structure on mutagenesis; (4) the regulation of mutational rates; and, (5) adaptive mutation in other microorganisms.
DNA Polymerases - Mutations are created when damaged DNA fails to be repaired and, instead, is replicated in its damaged state. However, replicative DNA polymerases are poor at synthesizing past a damaged base. Recently it has been shown that cells have special error-prone polymerases that bypass DNA lesions and produce mutations. When these polymerases displace accurate DNA polymerases on undamaged DNA, they may also contribute to spontaneous mutation. We have been investigating when and why error-prone polymerases appear in the cells. We find that under different sorts of stresses, DNA Polymerase IV is both induced and stabilized. These stresses include DNA damage, starvation, and heat shock. We hypothesize that the production of genetic variation can be advantageous to the population during stress. We are continuing to investigate: (1) what other stress responses may affect DNA polymerase IV; (2) how the stress responses regulate DNA polymerase IV; and, (3) the transcriptional and post-transcriptional regulation of other DNA polymerases and their subunits.
- Sladewski T.E., K.M. Hetrick, and P.L. Foster. 2011. Escherichia coli Rep DNA helicase and error-prone DNA polymerase IV interact physically and functionally. Molec. Microbiol. 80:524-541.
- Williams, A.B. and P.L. Foster. "Stress-Induced Mutagenesis." In A. Böck, R. et al. (eds.), EcoSal-Escherichia coli and Salmonella: Cellular and Molecular Biology. ASM Press, Washington, DC. In Press. [article]
- Storvik K.A. and P.L. Foster. 2011. The SMC-like protein complex SbcCD enhances DNA polymerase IV-dependent spontaneous mutation in Escherichia coli. J. Bacteriol. 193:660-669.
- Foster, P.L. 2011. Stress-induced mutagenesis in bacteria. Encyclopedia of Life Sciences. John Wiley & Sons, Ltd: Chichester. [article]
- Williams, A.B., K.M. Hetrick, and P.L. Foster. 2011. Double-strand break repair and Holliday junction processing are required for chromosome processing in stationary phase Escherichia coli cells. G3: Genes/Genomes/Genetics. 1:417-426. [article]
- Williams, A.B., K.M. Hetrick, and P.L. Foster 2010 Interplay of DNA repair, homologous recombination, and DNA polymerases in resistance to the DNA damaging agent 4-nitroquinoline-1-oxide in Escherichia coli. DNA Repair (Amst) 9:1090-1097.
- Storvik K.A. and P.L. Foster.2010 RpoS, the stress-response sigma factor, plays a dual role in the regulation of Escherichia coli's error-prone DNA polymerase IV. J Bacteriol. 192(14):3639-44. PMID: 20472798
- Stumpf, J.D., A.R. Poteete, and P.L. Foster. 2007 Amplification cannot account for adaptive mutation in Escherichia coli. J. Bacteriol. 189:2291-2299. PMID: 17209030
- Williams, A.B., and P.L. Foster. 2007 The Escherichia coli histone-like protein HU has a role in stationary phase adaptive mutation. Genetics 177:723-735. PMID: 17720921
- Foster, P.L. 2007 Stress-Induced Mutagenesis in Bacteria. Critical Reviews in Biochemistry and Molecular Biology. 42:373-397. PMID: 17917873
- Foster, P.L. 2006 Methods for Determining Spontaneous Mutation Rates. Methods in Enzymology 409: 195-213. PMID: 16045619
- Layton, J.C. and P.L. Foster 2005. Error-prone DNA polymerase IV is regulated by the heat-shock chaperone GroE in Escherichia coli. J. Bacteriol. 187:449-457. PMID: 15629916
- Stumpf, J.D. and P.L. Foster 2005 Polyphosphate kinase regulates error-prone replication by DNA polymerase IV in Escherichia coli. Molec. Microbiol. 57:751-761. PMID: 16045619
- Foster, P.L. 2004 Adaptive Mutation in Escherichia coli J. Bacteriol 186:4846-4852. PMID: 15262917
- Cairns J. and P.L. Foster. 2003. The risk of lethals for hypermutating bacteria in stationary phase. Genetics. 165:2317-2318. PMID: 14738105
- Layton, J.C. and P.L. Foster 2003 Error-prone DNA polymerase IV is controlled by the stress-response sigma factor, RpoS, in Escherichia coli. Molec. Microbiol. 50:549-561. PMID: 14617178
- Tompkins, J.D., J.L. Nelson, J.C. Hazel, H.L. Leugers, J.D. Stumpf, and P.L. Foster 2003. Error-prone polymerase, DNA polymerase IV, is responsible for transient hypermutation during adaptive mutation in Escherichia coli. J. Bacteriol. 185:3469-3472. PMID: 12754247
- Rodriguez, C, J. Tompkins, J. Hazel, and P.L. Foster 2002 Induction of a DNA nickase in the presence of its target site stimulates adaptive mutation in Escherichia coli. J. Bacteriol. 184:5599-5608 . PMID: 12270817