THE STRUCTURE AND FUNCTIONS OF THE HAP1 REF-1 PROTEIN/

The HAP1/Ref-1 (hereafter referred to as HAP1) protein is a nuclear en zyme that apparently performs two distinct roles in the cellular defen se against oxidative stress. One well-established role is in the repai r of a variety of lesions induced in DNA either by spontaneous hydroly sis or by reactive oxygen species (ROS). This function has been charac terized in great detail and the roles played by individual active site amino acid residues have been defined. The second role, which was ide ntified only relatively recently and is still not characterized in det ail, is to regulate the DNA binding activity of a group of nuclear fac tors. This second role proceeds via the modification of the oxidation/ reduction (redox) state of a cysteine residue in the target protein, a lthough the mechanism by which this is achieved remains to be elucidat ed. In this article, we shall review the latest knowledge on the relat ionship between structure and the dual functions of HAP1, and we will seek to explain in detail the roles played by several individual amino acid residues in the catalytic function of the HAP1 protein.