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• W3135105281 startingPage "103078" @default.
• W3135105281 abstract "Mitochondrion is an essential organelle in malaria parasite and its DNA must be maintained for optimal function during its complex life cycle. Base excision repair is one of the major pathways by which this is achieved. Apurinic/apyrimidinic (AP) endonucleases are important components of this pathway as they create a nick at the 5′-phosphodiester bond in the AP site and generate free 5′-phosphate and 3′-hydroxyl groups. Two class II AP endonucleases (Apn1 and Ape1) have been annotated in the Plasmodium berghei genome. Using reverse genetic approaches, we provide direct evidence that Apn1 is exclusively localized to the mitochondria of P. berghei. Surprisingly, our gene deletion study revealed a completely dispensable role of Apn1 for the entirety of the P. berghei life cycle. Apn1− parasites were found to successfully grow in the blood. They were transmitted normally to the mosquito midguts and salivary glands. Sporozoites obtained from the salivary glands were infective and achieved similar patency as WT. Our results help emphasize the non-availability of this enzyme as a plausible drug target. We also emphasize the importance of genetic validation of antimalarial drug targets before furthering them down the drug discovery pipeline." @default.
• W3135105281 created "2021-03-15" @default.
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• W3135105281 date "2021-05-01" @default.
• W3135105281 modified "2023-09-27" @default.
• W3135105281 title "Mitochondrial apurinic/apyrimidinic endonuclease Apn1 is not critical for the completion of the Plasmodium berghei life cycle" @default.
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• W3135105281 doi "https://doi.org/10.1016/j.dnarep.2021.103078" @default.
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