Nuclear‐encoded DnaJ homologue of Plasmodium falciparum interacts with replication ori of the apicoplast genome |
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Authors: | Ambrish Kumar Aiman Tanveer Subir Biswas Edupuganti V. S. Raghu Ram Ankit Gupta Bijay Kumar Saman Habib |
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Affiliation: | 1. Present address: Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, USA.;2. Division of Molecular and Structural Biology, Central Drug Research Institute, Lucknow 226001, India. |
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Abstract: | The apicoplast of Plasmodium falciparum carries a 35 kb circular genome (plDNA) that replicates at the late trophozoite stage of the parasite intraerythocytic cycle. plDNA replication proceeds predominantly via a d ‐loop/bi‐directional ori mechanism with replication ori localized within inverted repeat region. Although replication of the apicoplast genome is a validated drug target, the proteins involved in the replication process are only partially characterized. We analysed DNA–protein interactions at a plDNA replication ori region and report the identification of a nuclear‐encoded DnaJ homologue that binds directly to ori elements of the plDNA molecule. PfDnaJA interacted with the minor groove of the DNA double‐helix and recognized a 13 bp sequence within the ori. Inhibition of binding with anti‐PfDnaJA antibodies confirmed identity of the protein in DNA‐binding experiments with organellar protein fractions. The DNA‐binding domain of the ~69 kDa PfDnaJA lay within the N‐terminal 38 kDa region that carries DnaJ signature motifs. In contrast to PfDnaJA in parasite organellar fractions, the recombinant protein interacted with DNA in a sequence non‐specific manner. Our results suggest a role for PfDnaJA in replication/repair of the apicoplast genome. |
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