Haltiwanger B M, Karpinich N O, Taraschi T F
Department of Microbiology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Biochem J. 2000 Jan 1;345 Pt 1(Pt 1):85-9.
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.
我们已经报道，人类疟原虫恶性疟原虫通过长片段碱基切除修复（BER）途径修复DNA上的无嘌呤/无嘧啶（AP）位点。这种生物学特性与哺乳动物细胞不同，哺乳动物细胞主要通过依赖DNA聚合酶β的单核苷酸补片BER途径修复AP位点。作为鉴定参与寄生虫DNA BER途径的酶并对其进行生化特性分析的起点，我们选择对恶性疟原虫无细胞裂解物中的AP核酸内切酶活性进行特性分析。有证据表明寄生虫裂解物中存在II类、依赖Mg(2+)和不依赖Mg(2+)的AP核酸内切酶。对疟原虫中AP位点处理过程的研究将为长片段BER途径提供新的信息；如果它们与人类宿主中的途径不同，可能会为抗疟疾化疗提供新的靶点。
