Characterization of class II apurinic/apyrimidinic endonuclease activitiesin the human malaria parasite, Plasmodium falciparum

We have reported that the human malaria parasite, Plasmodium falciparum, re pairs apurinic/apyrimidinic (AP) sites on DNA by a long-patch base excision repair (BER) pathway. This biology is different from that in mammalian cel ls, which predominantly repair AP sites by a DNA-polymerase-beta-dependent, one-nucleotide patch BER pathway. As a starting point for the identificati on and biochemical characterization of the enzymes involved in the parasite DNA BER pathway, we chose characterization of the AP endonuclease activity in a P. falciparum cell-free lysate. Evidence is provided for the presence of class II, Mg2+-dependent and independent AP endonucleases in the parasi te lysate. The investigation of the processing of AP sites in Plasmodium wi ll provide new information about long-patch BER pathways; if they are diffe rent from those in the human host they might provide a new target for anti- malarial chemotherapy.