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Mammalian cells repair apurinic/apyrimidinic (AP) sites in DNA by two distinct pathways: a polymerase beta (pol beta)-dependent, short- (one nucleotide) patch base excision repair (BER) pathway, which is the major route, and a PCNA-dependent, long- (several nucleotide) patch BER pathway. The ability of a cell-free lysate prepared from asexual Plasmodium falciparum malaria parasites to remove uracil and repair AP sites in a variety of DNA substrates was investigated. We found that the lysate contained uracil DNA glycosylase, AP endonuclease, DNA polymerase, flap endonuclease, and DNA ligase activities. This cell-free lysate effectively repaired a regular or synthetic AP site on a covalently closed circular (ccc) duplex plasmid molecule or a long (382 bp), linear duplex DNA fragment, or a regular or reduced AP site in short (28 bp), duplex oligonucleotides. Repair of the AP sites in the various DNA substrates involved a long-patch BER pathway. This biology is different from mammalian cells, yeast, Xenopus, and Escherichia coli, which predominantly repair AP sites by a one-nucleotide patch BER pathway. The apparent absence of a short-patch BER pathway in P. falciparum may provide opportunities to develop antimalarial chemotherapeutic strategies for selectively damaging the parasites in vivo and will allow the characterization of the long-patch BER pathway without having to knock-out or inactivate a short-patch BER pathway, which is necessary in mammalian cells.


Journal article



Publication Date





763 - 772


Animals, Binding Sites, Carbon-Oxygen Lyases, Cell-Free System, DNA Glycosylases, DNA Repair, DNA, Circular, DNA, Protozoan, DNA-(Apurinic or Apyrimidinic Site) Lyase, Deoxyribonuclease IV (Phage T4-Induced), Endodeoxyribonucleases, Enzyme Activation, Escherichia coli Proteins, Flap Endonucleases, Humans, Malaria, Falciparum, N-Glycosyl Hydrolases, Plasmids, Plasmodium falciparum, Uracil-DNA Glycosidase