Stress-induced mutation via DNA breaks in Escherichia coli: a molecular mechanism with implications for evolution and medicine.
Evolutionary theory assumed that mutations occur constantly, gradually, and randomly over time. This formulation from the "modern synthesis" of the 1930s was embraced decades before molecular understanding of genes or mutations. Since then, our labs and others have elucidated mutation mechanisms activated by stress responses. Stress-induced mutation mechanisms produce mutations, potentially accelerating evolution, specifically when cells are maladapted to their environment, that is, when they are stressed. The mechanisms of stress-induced mutation that are being revealed experimentally in laboratory settings provide compelling models for mutagenesis that propels pathogen-host adaptation, antibiotic resistance, cancer progression and resistance, and perhaps much of evolution generally. We discuss double-strand-break-dependent stress-induced mutation in Escherichia coli. Recent results illustrate how a stress response activates mutagenesis and demonstrate this mechanism's generality and importance to spontaneous mutation. New data also suggest a possible harmony between previous, apparently opposed, models for the molecular mechanism. They additionally strengthen the case for anti-evolvability therapeutics for infectious disease and cancer.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. smr@bcm.edu
Susan M
SM
Rosenberg
Chandan
C
Shee
Ryan L
RL
Frisch
P J
PJ
Hastings
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics; D015195:Drug Design; D004352:Drug Resistance, Microbial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics* / Q000502:physiology; D029968:Escherichia coli Proteins / Q000502:physiology; D019143:Evolution, Molecular; D006801:Humans; D016296:Mutagenesis; D012641:Selection, Genetic; D013312:Stress, Physiological
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins