Electrochemical study of oxetanes mimicking DNA (6-4) photoproducts gives new insight into the repair mechanism by ( 6-4) photolyase. Both electrochemical oxidation and electrochemical reduction at carbon electrodes lead to the cleavage of the oxetanes in a retro-Paterno-Buchi sequence. Within the family of compounds investigated and the range of driving forces offered, transient formation of unstable radical ions is observed, for both oxidative and reductive cleavage. Taking advantage of the electrochemical signature of these mimics, enzymatic assay with Escherichia coli CPD photolyase coupled to electrochemical monitoring of the reaction brings evidence that enzymatic repair of (6-4) DNA photoproducts does involve a catalytic dissociative electron-transfer mechanism at the level of an oxetane intermediate.