Expression and subcellular localization of human AP endonuclease 1 (HAP1/Ref-1) protein: a basis for its role in human disease

Aims: Human AP endonuclease 1 (HAP1) plays a major role in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA by catalysing hydrolytic cleavage of the phosphodiester backbone 5′ to the site. HAP1 is also known to be a potent reduction–oxidation (redox) factor, regulating the binding activity of a number of transcription factors. The purpose of the present study was to examine the expression of HAP‐1 in a wide range of human tissues. Methods and results Using a recently developed specific rabbit polyclonal antibody, we performed immunohistochemistry on paraffin‐embedded tissue material. Nuclear staining was detected in crypt cells of the small and large intestine, epithelial cells of breast ducts, basal cells of the skin, alveolar cells of the lung, lymphocytes of the marginal zone of the spleen, in the surface epithelium and stromal cells of the ovary and the transitional epithelium of the bladder. Unexpectedly for a presumed nuclear protein, the staining pattern in some cell populations was mainly cytoplasmic (e.g. superficial cells of gastrointestinal tract, Langerhans cells, Leydig cells and spermatocytes, epithelium of the prostate glands), or both cytoplasmic and nuclear (e.g. epithelial cells of thymus, follicular thyroid cells, parietal cells of the stomach, glandular epithelial cells of the cervix, epithelial cells of exocrine pancreas). Conclusion This differential expression in a wide spectrum of cells is indicative of a potential multifunctional action of HAP1, not necessarily restricted to a role in the nucleus.