Uracil moieties in Plasmodium falciparum genomic DNA

Molnár, Petra and Marton, Lívia and Izrael, Richard and Pálinkás, Hajnalka L. and G. Vértessy, Beáta (2018) Uracil moieties in Plasmodium falciparum genomic DNA. FEBS OPEN BIO, 8. pp. 1763-1772. ISSN 2211-5463

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Abstract

Plasmodium falciparum parasites undergo multiple genome duplication events during their development. Within the intraerythrocytic stages, parasites encounter an oxidative environment and DNA synthesis necessarily proceeds under these circumstances. In addition to these conditions, the extreme AT bias of the P. falciparum genome poses further constraints for DNA synthesis. Taken together, these circumstances may allow appearance of damaged bases in the PlasmodiumDNA. Here, we focus on uracil that may arise in DNA either via oxidative deamination or thymine-replacing incorporation. We determine the level of uracil at the ring, trophozoite, and schizont intraerythrocytic stages and evaluate the base-excision repair potential of P. falciparum to deal with uracil-DNA repair. We find approximately 7–10 uracil per million bases in the different parasite stages. This level is considerably higher than found in other wild-type organisms from bacteria to mammalian species. Based on a systematic assessment of P. falciparum genome and transcriptome databases, we conclude that uracil-DNA repair relies on one single uracil-DNA glycosylase and proceeds through the long-patch base-excision repair route. Although potentially efficient, the repair route still leaves considerable level of uracils in parasite DNA, which may contribute to mutation rates in P. falciparum. © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

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