The ionizing radiation (IR) dose that yields 20% survival (D 20 ) of Shewanella oneidensis MR-1 is lower by factors of 20 and 200 than those for Escherichia coli and Deinococcus radiodurans, respectively. Transcriptome analysis was used to identify the genes of MR-1 responding to 40 Gy (D 20 ). We observed the induction of 170 genes and repression of 87 genes in MR-1 during a 1-h recovery period after irradiation. The genomic response of MR-1 to IR is very similar to its response to UV radiation (254 nm), which included induction of systems involved in DNA repair and prophage synthesis and the absence of differential regulation of tricarboxylic acid cycle activity, which occurs in IR-irradiated D. radiodurans. Furthermore, strong induction of genes encoding antioxidant enzymes in MR-1 was observed. DNA damage may not be the principal cause of high sensitivity to IR, considering that MR-1 carries genes encoding a complex set of DNA repair systems and 40 Gy IR induces less than one double-strand break in its genome. Instead, a combination of oxidative stress, protein damage, and prophage-mediated cell lysis during irradiation and recovery might underlie this organism's great sensitivity to IR.Ionizing radiation (IR) is potentially lethal and mutagenic to all organisms. The cellular response to IR is complex due to the variety of targets in a cell. IR can damage cellular components through direct deposition of radiation energy into biomolecules and also indirectly by generating reactive oxygen species (ROS). Hydrogen peroxide (H 2 O 2 ) and hydroxyl radicals (HO·) are major oxidizing species produced by the radiolysis of water, and superoxide ions (O 2 · Ϫ ) are formed in the presence of dissolved oxygen (8,24,25,27,28).Generally, the cytotoxic and mutagenic effects induced by IR are thought to be the result of DNA damage caused during the course of irradiation, which includes single-strand breaks (SSB), double-strand breaks (DSB), base modification, abasic sites, and sugar modification (11,27). The amounts of DNA damage caused by given doses of IR for different bacteria are very similar, although the range of IR resistance levels is large. The dissimilatory metal ion-reducing Shewanella oneidensis strain MR-1 is extremely sensitive to IR: e.g., 90% of MR-1 cells are killed by less than one DSB in the genome (4). S. oneidensis is also one of the most UV-and desiccation-sensitive organisms reported (4,22). The IR resistance of MR-1 is about 20 times less than that of Escherichia coli and about 200 times less than that of Deinococcus radiodurans (4). It is unclear why S. oneidensis MR-1 is exceptionally sensitive to radiation.Since more than 80% of IR energy deposited in cells results in the ejection of electrons from water, a large amount of ROS is produced in cells exposed to IR (8,25