The role of transcription factors in the regulation of gene expression is well established. Although the activity of these factors can be regulated by phosphorylation,evidence has indicated regulation of DNA binding mediated by changes in reduction-oxidation (redox) status. Mutational analysis has identified a single conserved cysteine residue mapping within the DNA binding domains of Fos and Jun. Chemical oxidation or modification of this cysteine residue inhibits the DNA binding activity of Fos and Jun. A similar mode of regulation has been recently proposed for other nuclear transcription factors. Oxidation is reversible by these compounds or by a cellular redox/DNA repair protein identified originally as Ref-1 (redox factor 1). Ref-1 is identical to a previously characterized DNA repair enzyme designated HAP1, APE or APEX.