REGULATED EXPRESSION OF APE APURINIC ENDONUCLEASE MESSENGER-RNA DURING WOUND-HEALING IN PORCINE EPIDERMIS

Abasic (AP) sites in DNA are cytotoxic and mutagenic and their repair is initiated by AP endonucleases. The major AP endonuclease of mammali an cells is encoded by the APE gene. Ape protein has also been propose d to modulate the activity of some transcription factors independently of its AP endonuclease activity. We investigated whether APE expressi on is coordinated with cell division, which could diminish mutagenesis . The level of APE mRNA was followed during wound healing in porcine e pidermis, in which surgical wounding prompts rapid cell proliferation followed by a differentiation program to regenerate normal skin. In si tu hybridization with a probe from human APE cDNA revealed strongly de creased expression in rapidly proliferating migrating cells during the first 1-3 days following wounding, succeeded by sharply increased APE expression that exceeded the pre-wounding levels by days 9-17. These changes were not observed in the surrounding undamaged tissue. In cont rast to the foregoing in vivo results, APE expression in cultured prim ary human fibroblasts (IMR90) or myeloid leukemia cells (K562) was not coordinated with cell division. This biphasic APE expression during w ound healing could relate to transcription factor regulation or it cou ld allow unhindered DNA synthesis or prepare the developing epidermis to handle DNA damage. However, if transient under-expression of APE-en coded repair enzyme does occur, it might render regenerating skin espe cially vulnerable to mutagenesis during the cell proliferation phase.