Authors: Galhardo, Rodrigo; Hastings, P. J.; Rosenberg, Susan

Source: Critical Reviews in Biochemistry and Molecular Biology, Volume 42, Number 5, September 2007 , pp. 399-435(37)

Publisher: Informa Healthcare

Abstract:

Our concept of a stable genome is evolving to one in which genomes are plastic and responsive to environmental changes. Growing evidence shows that a variety of environmental stresses induce genomic instability in bacteria, yeast, and human cancer cells, generating occasional fitter mutants and potentially accelerating adaptive evolution. The emerging molecular mechanisms of stress-induced mutagenesis vary but share telling common components that underscore two common themes. The first is the regulation of mutagenesis in time by cellular stress responses, which promote random mutations specifically when cells are poorly adapted to their environments, i.e., when they are stressed. A second theme is the possible restriction of random mutagenesis in genomic space, achieved via coupling of mutation-generating machinery to local events such as DNA-break repair or transcription. Such localization may minimize accumulation of deleterious mutations in the genomes of rare fitter mutants, and promote local concerted evolution. Although mutagenesis induced by stresses other than direct damage to DNA was previously controversial, evidence for the existence of various stress-induced mutagenesis programs is now overwhelming and widespread. Such mechanisms probably fuel evolution of microbial pathogenesis and antibiotic-resistance, and tumor progression and chemotherapy resistance, all of which occur under stress, driven by mutations. The emerging commonalities in stress-induced-mutation mechanisms provide hope for new therapeutic interventions for all of these processes.

Keywords: adaptive mutation; evolution; mutation rates; error-prone DNA polymerases; stress responses; recombination; DNA repair; SOS response; σS; RpoS; cancer; genome instability; microbial pathogenesis; antibiotic resistance

Document Type: Research article

DOI: http://dx.doi.org/10.1080/10409230701648502

Affiliations: 1: Department of Molecular and Human Genetics, Houston, Texas, USA,Departments of Biochemistry and Molecular Biology, and Molecular Virology and Microbiology, Houston, Texas, USA,The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston,

Publication date: 2007-09-01

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