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Controlling Mutation: Intervening in Evolution as a Therapeutic Strategy 

Authors: Ryan T. Cirz a; Floyd E. Romesberg a
Affiliation:   a The Scripps Research Institute, La Jolla, California, USA
DOI: 10.1080/10409230701597741
Publication Frequency: 6 issues per year
Published in: journal Critical Reviews in Biochemistry and Molecular Biology, Volume 42, Issue 5 September 2007 , pages 341 - 354
Formats available: HTML (English) : PDF (English)
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Abstract

Mutation is the driving force behind many processes linked to human disease, including cancer, aging, and the evolution of drug resistance. Mutations have traditionally been considered the inevitable consequence of replicating large genomes with polymerases of finite fidelity. Observations over the past several decades, however, have led to a new perspective on the process of mutagenesis. It has become clear that, under some circumstances, mutagenesis is a regulated process that requires the induction of pro-mutagenic enzymes and that, at least in bacteria, this induction may facilitate evolution. Herein, we review what is known about induced mutagenesis in bacteria as well as evidence that it contributes to the evolution of antibiotic resistance. Finally, we discuss the possibility that components of induced mutation pathways might be targeted for inhibition as a novel therapeutic strategy to prevent the evolution of antibiotic resistance.
Keywords: induced mutation; antibiotic resistance; SOS response
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