Special mechanisms of mutation are induced in bacteria, yeast and human cells under growth-limiting stress, under the control of stress responses. These mechanisms increase genetic diversity and potentially the ability to evolve specifically when cells are maladapted to their environment, i.e., when they are stressed. Stress-synchronous- mutation mechanisms may provide superior models for genetic changes that drive pathogen-host adaptation, antibiotic resistance, aging, cancer progression and therapy- resistance mechanisms, and possibly much of evolution generally. This project is an investigation of three molecular mechanisms of stress-synchronous genomic instability in E. coli, with a goal of finding common themes. Because the mechanisms studied have common components with several other (less understood) mechanisms of stress- synchronous mutation, the results should provide both important models for understanding the problems listed above and specific tools for combating antibiotic resistance.

Public Health Relevance

This project will provide new ways to approach and combat problems of development of cancers, evolution of cancer-chemotherapy resistance, aging, microbial pathogenesis and antibiotic resistance among other serious problems in human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM053158-15A1
Application #
8186943
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Janes, Daniel E
Project Start
1995-09-30
Project End
2015-07-31
Budget Start
2011-09-01
Budget End
2012-07-31
Support Year
15
Fiscal Year
2011
Total Cost
$583,745
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Fitzgerald, Devon M; Hastings, P J; Rosenberg, Susan M (2017) Stress-Induced Mutagenesis: Implications in Cancer and Drug Resistance. Annu Rev Cancer Biol 1:119-140
Nehring, Ralf B; Gu, Franklin; Lin, Hsin-Yu et al. (2016) An ultra-dense library resource for rapid deconvolution of mutations that cause phenotypes in Escherichia coli. Nucleic Acids Res 44:e41
Barreto, Brittany; Rogers, Elizabeth; Xia, Jun et al. (2016) The Small RNA GcvB Promotes Mutagenic Break Repair by Opposing the Membrane Stress Response. J Bacteriol 198:3296-3308
Dohrmann, Paul R; Correa, Raul; Frisch, Ryan L et al. (2016) The DNA polymerase III holoenzyme contains ? and is not a trimeric polymerase. Nucleic Acids Res 44:1285-97
Moore, Jessica M; Magnan, David; Mojica, Ana K et al. (2015) Roles of Nucleoid-Associated Proteins in Stress-Induced Mutagenic Break Repair in Starving Escherichia coli. Genetics 201:1349-62
Gibson, Janet L; Lombardo, Mary-Jane; Aponyi, Ildiko et al. (2015) Atypical Role for PhoU in Mutagenic Break Repair under Stress in Escherichia coli. PLoS One 10:e0123315
Bos, Julia; Zhang, Qiucen; Vyawahare, Saurabh et al. (2015) Emergence of antibiotic resistance from multinucleated bacterial filaments. Proc Natl Acad Sci U S A 112:178-83
Rosenberg, Susan M; Queitsch, Christine (2014) Medicine. Combating evolution to fight disease. Science 343:1088-9
Wimberly, Hallie; Shee, Chandan; Thornton, P C et al. (2013) R-loops and nicks initiate DNA breakage and genome instability in non-growing Escherichia coli. Nat Commun 4:2115
Walker, Sara Imari; Callahan, Benjamin J; Arya, Gaurav et al. (2013) Evolutionary dynamics and information hierarchies in biological systems. Ann N Y Acad Sci 1305:1-17

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