The crosslinking of proteins of DNA has been demonstrated in cells treated by ultraviolet radiation, x-rays and various chemicals. The natural accumulation of this type of damage has also been proposed as a mechanism for aging and carcinogenesis. Although crosslinks have been detected by physical-chemical techniques in irradiated DNA and in DNA extracted from the tissues of aged animals, the biological significance of such crosslinks has not been adequately investigated. This research will: 1) Evaluate the significance of UV-induced DNA-protein crosslinks in the biological inactivation of viral DNA; 2) determine the extent to which the open "breathing" regions of DNA affect its UV sensitivity and, in particular, its sensitivity to protein crosslink formation; 3) examine the effects of carcinogens and mutagens on the UV sensitivity of DNA-protein complexes and evaluate the transfection system as a possible simple assay system for potential carcinogens and mutagens; and 4) attempt to identify a bacterial enzyme system capable of detecting and repairing regions of DNA crosslinked to proteins.