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 ap urinic/apyrimidinic (AP) sites in cellular DNA by catalysing hydrolytic cle avage of the phosphodiester backbone 5' to the site. HAP1 is also known to be a potent reduction-oxidation (redox) factor, regulating the binding acti vity 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 mat erial. Nuclear staining was detected in crypt cells of the small and large intestine, epithelial cells of breast ducts, basal cells of the skin, alveo lar cells of the lung, lymphocytes of the marginal zone of the spleen, in t he surface epithelium and stromal cells of the ovary and the transitional e pithelium of the bladder, Unexpectedly for a presumed nuclear protein, the staining pattern in some cell populations was mainly cytoplasmic (e.g. supe rficial 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, pariet al cells of tl-le stomach, glandular epithelial cells of the cervix, epithe lial cells of exocrine pancreas). Conclusion: This differential expression in a wide spectrum of cells is ind icative of a potential multifunctional action of HAP1, not necessarily rest ricted to a role in the nucleus.