Molecular mechanisms of stress-induced mutation in E. coli

描述(申请人提供)：在生长限制压力下，在细菌和酵母中诱导特殊的突变机制，导致遗传不稳定，偶尔，可能加速进化的适应性突变。这些应激诱导的突变机制可能为促进衰老的基因变化、癌症形成的遗传不稳定性、化疗耐药性的进展和获得、病原体对宿主防御和抗生素的耐药性以及可能的大部分进化提供了更好的模型。这项建议侧重于在大肠杆菌模型中理解应激诱导遗传不稳定性的分子机制。由于所研究的机制与其他几种(较少被理解的)应激诱导突变机制有共同的成分，这些结果应该提供一个重要的通用模型。

DESCRIPTION (provided by applicant): Special mechanisms of mutation are induced in bacteria and yeasts under growth-limiting stress causing genetic instability, and occasionally, adaptive mutations that may speed evolution. These stress-induced mutation mechanisms may provide superior models for genetic changes that promote aging, genetic instability underlying cancer formation, progression and acquisition of chemotherapy resistance, resistance of pathogens to host defenses and antibiotics, and possibly much of evolution generally. This proposal focuses on understanding the molecular mechanisms of stress-induced genetic instability in an E. coli model. Because the mechanism studied has common components with several other (less understood) mechanisms of stress-induced mutation, the results should provide an important general model.