title: Characterization of class II apurinic/apyrimidinic endonuclease activities in the human malaria parasite, Plasmodium falciparum.
abstract: We have reported that the human malaria parasite, Plasmodium falciparum, repairs apurinic/apyrimidinic (AP) sites on DNA by a long-patch base excision repair (BER) pathway. This biology is different from that in mammalian cells, which predominantly repair AP sites by a DNA-polymerase-beta-dependent, one-nucleotide patch BER pathway. As a starting point for the identification 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, Mg(2+)-dependent and independent AP endonucleases in the parasite lysate. The investigation of the processing of AP sites in Plasmodium will provide new information about long-patch BER pathways; if they are different from those in the human host they might provide a new target for anti-malarial chemotherapy.
authors.affiliation: Department of Microbiology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Haltiwanger
authors.forename: N O
authors.initials: NO
authors.lastname: Karpinich
authors.forename: T F
authors.initials: TF
authors.lastname: Taraschi
mesh_terms: D000818:Animals; D001483:Base Sequence; D019757:Carbon-Oxygen Lyases / Q000145:classification* / Q000378:metabolism*; D002474:Cell-Free System; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D006801:Humans; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D009838:Oligodeoxyribonucleotides; D043223:Deoxyribonuclease IV (Phage T4-Induced); D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D008274:Magnesium