Germination and outgrowth are critical steps for returning Bacillus subtilis spores to life. However, oxidative stress due to full hydration of the spore core during germination and activation of metabolism in spore outgrowth may generate oxidative DNA damage that in many species is processed by apurinic/apyrimidinic (AP) endonucleases. B. subtilis spores possess two AP endonucleases, Nfo and ExoA; the outgrowth of spores lacking both of these enzymes was slowed, and the spores had an elevated mutation frequency, suggesting that these enzymes repair DNA lesions induced by oxidative stress during spore germination and outgrowth. Addition of H 2 O 2 also slowed the outgrowth of nfo exoA spores and increased the mutation frequency, and nfo and exoA mutations slowed the outgrowth of spores deficient in either RecA, nucleotide excision repair (NER), or the DNA-protective ␣/␤-type small acid-soluble spore proteins (SASP). These results suggest that ␣/␤-type SASP protect DNA of germinating spores against damage that can be repaired by Nfo and ExoA, which is generated either spontaneously or promoted by addition of H 2 O 2 . The contribution of RecA and Nfo/ExoA was similar to but greater than that of NER in repair of DNA damage generated during spore germination and outgrowth. However, nfo and exoA mutations increased the spontaneous mutation frequencies of outgrown spores lacking uvrA or recA to about the same extent, suggesting that DNA lesions generated during spore germination and outgrowth are processed by Nfo/ExoA in combination with NER and/or RecA. These results suggest that Nfo/ExoA, RecA, the NER system, and ␣/␤-type SASP all contribute to the repair of and/or protection against oxidative damage of DNA in germinating and outgrowing spores.Due to their ability to survive during long periods of dormancy, spores of Bacillus subtilis are an excellent model system in which to study the consequences of exposure to environmental factors that can cause DNA damage. Physical and chemical factors, including UV-A and -B from sunlight, high temperatures, desiccation, and oxidizing chemicals, such as hydrogen peroxide, have the potential to cause damage to dormant spore DNA (13, 15). However, spores of the genus Bacillus counter these potential damaging agents with a number of factors to maintain the integrity of the genome. These factors include (i) the spore coats, (ii) the low water content in the spore core, (iii) the low permeability of the spore's inner membrane to hydrophilic small molecules, and (iv) the saturation of spore DNA with ␣/␤-type small acid-soluble spore proteins (SASP) (13,28,29,31). The ␣/␤-type SASP play the most direct role in protecting spore DNA from a variety of types of damage, including depurination-depyrimidination and hydroxyl radical-induced backbone cleavage. As a consequence, these proteins make major contributions to spore resistance to heat and oxidizing agents (13, 31). The ␣/␤-type SASP are also a major factor in the high resistance of B. subtilis spores to UV light (13,14,28,29,31). H...