Transcription Associated Mutagenesis in Cells Under Conditions of Arrested Growth

Eduardo Robleto, Ph.D. (University of Nevada, Las Vegas)

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The study of genetic programs that enhance diversity during stressful or non-dividing conditions of organisms that undergo cell differentiation is highly relevant to human health, it provides insights on how pathogenic organisms mutate and overcome natural and aided defenses to infection. Also, such a study is a paradigm to dissect the molecular basis of neoplasms and the underlying mechanism(s) of the evolutionary process. While current research models have focused on DNA metabolism in non-growing conditions, little attention has been drawn to programs that enhance genetic diversity via RNA metabolism. The involvement of transcription in genetic programs is stimulating not only because it connects cell physiology and mutagenic processes, but it also provides a solution to the conundrum of how stress might increase genetic diversity without causing genetic load (the point at which a species can no longer exist because of the accumulation of deleterious mutations). Eduardo Robleto examines genetic mechanisms in cells under stress or non-dividing conditions in Bacillus subtilis, a Gram positive model organism. B. subtilis provides an accessible paradigm for the study of the formation of mutant transcripts, the control of cell differentiation and stress-induced mutagenesis, the basis of the neoplastic process.