The genome of a radiation-resistant bacterium, Deinococcus radiodurans, contains one uvsE gene and two uvrA genes, uvrA1 and uvrA2. Using a series of mutants lacking these genes, we determined the biological significance of these components to UV resistance. The UV damage endonuclease (UvsE)-dependent excision repair (UVER) pathway and UvrA1-dependent pathway show some redundancy in their function to counteract the lethal effects of UV. Loss of these pathways does not cause increased sensitivity to UV mutagenesis, suggesting either that these pathways play no function in inducing mutations or that there are mechanisms to prevent mutation other than these excision repair pathways. UVER efficiently removes both cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) from genomic DNA. In contrast, the UvrA1 pathway does not significantly contribute to the repair of CPDs but eliminates 6-4PPs. Inactivation of uvrA2 does not result in a deleterious effect on survival, mutagenesis, or the repair kinetics of CPDs and 6-4PPs, indicating a minor role in resistance to UV. Loss of uvsE, uvrA1, and uvrA2 reduces but does not completely abolish the ability to eliminate CPDs and 6-4PPs from genomic DNA. The result indicates the existence of a system that removes UV damage yet to be identified.