Stress-Induced Mutagenesis

The discovery of stress-induced mutagenesis has changed ideas about mutation and evolution, and revealed mutagenic programs that differ from standard spontaneous mutagenesis in rapidly proliferating cells. The stress-induced mutations occur during growth-limiting stress, and can include adaptive mutations that allow growth in the otherwise growth-limiting environment. The stress responses increase mutagenesis specifically when cells are maladapted to their environments, i.e. are stressed, potentially accelerating evolution then. The mutation mechanism also includes temporary suspension of post-synthesis mismatch repair, resembling mutagenesis characteristic of some cancers. Stress-induced mutation mechanisms may provide important models for genome instability underlying some cancers and genetic diseases, resistance to chemotherapeutic and antibiotic drugs, pathogenicity of microbes, and many other important evolutionary processes.

This book covers pathways of stress-induced mutagenesis in all systems. The principle focus is mammalian systems, but much of what is known of these pathways comes from non-mammalian systems.

The discoveries of stress-induced mutation and epigenetic inheritance have challenged the claim of independence between the evolutionary forces of mutation and selection. In “Stress-Induced Mutagenesis”, leading experts provide the key evidence for and the molecular details of stress-induced genetic and epigenetic mutation, integrating cross-disciplinary observations from a number of species and biological systems, including human. The observations have vast implications for evolutionary biology but also for human medicine. A comprehensive understanding of stress-induced mutagenesis and the processes underlying evolvability, will enable gains in the treatment and management of cancer, as well as other human disorders that result from damaged or unstable genomes.