DNA base excision repair in human malaria parasites is predominantly by a long-patch pathway

Biochemistry. 2000 Feb 1;39(4):763-72. doi: 10.1021/bi9923151.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


  • DNA, Circular
  • DNA, Protozoan
  • Escherichia coli Proteins
  • Endodeoxyribonucleases
  • Flap Endonucleases
  • FEN1 protein, human
  • Deoxyribonuclease IV (Phage T4-Induced)
  • endonuclease IV, E coli
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • Uracil-DNA Glycosidase
  • Carbon-Oxygen Lyases
  • DNA-(Apurinic or Apyrimidinic Site) Lyase