Surviving Ionizing Radiation: General Stress Response and Mechanisms for the Prevention and Repair of DNA Damage in <em>Halobacterium</em> sp. str. NRC-1
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The effects of ionizing radiation on the extremely halophilic Archaeon <em>Halobacterium</em> sp. str. NRC-1 can be divided into three central themes: protection from oxidative damages, response to ionizing radiation, and repair of DNA double strand breaks (DSBs). Intracellular salts used to maintain osmotic balance in the hypersaline conditions <em>Halobacterium</em> cells require are shown in this study to provide <em>in vivo</em> protection from oxidative damages through the scavenging of hydroxyl radicals produced from the radiolysis of water by gamma radiation. These results highlight both the importance of the intracellular environment in determining radiation resistance and the multiplicity of pathways resulting in radiation resistance that can be utilized by various microbes resulting from their adaptations to common environmental stresses such as desiccation. The global stress response to gamma radiation was measured using both genomic and proteomic methods. The resulting systems view reveals cooperation amongst several cellular processes including DNA repair, increased protein turnover, apparent shifts in metabolism to favor nucleotide biosynthesis and an overall effort to repair oxidative damage. Further, we demonstrate the importance of time dimension while correlating mRNA and protein levels and suggest that steady state comparisons may be misleading while assessing dynamics of genetic information processing across transcription and translation. The repair of DNA DSBs incurred after exposure to gamma radiation was examined in greater detail. The <em>in vivo</em> role of the Mre11/Rad50 complex was determined in an archaeal model system to determine if these proteins performed the same role in homologous recombination repair as their eukaryotic homologs. Deletion of <em>mre11</em> was found to reduce the rate of DSB repair, but not the overall survival of the cells. Taken together, the data presented here provide a halophilic model for radiation resistance that shares some common elements with other radiation resistant organisms such as <em>Deinococcus radiodurans</em> while presenting alternative mechanisms specific to extreme halophiles.