PREX: the plastidic DNA replication/repair enzyme complex of the apicomplexan parasites

Mukhopadhyay, Arunima (2006) PREX: the plastidic DNA replication/repair enzyme complex of the apicomplexan parasites. PhD thesis, University of Glasgow.

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Plasmodium and Toxoplasma nuclear genomes possess an ORF for a putative protein which contains domains homologous to the T7 bacteriophage primase-helicase like Twinkle enzyme and the prokaryotic family A polymerase enzyme. It has been hypothesised that this nuclear encoded protein may be responsible for the replication and repair of the apicoplast genome. Thus it was named PREX (Plastidic DNA Replication/Repair Enzyme complex).

In Plasmodium falciparum the ORF (Pfprex) is 6,051 bp with no introns. RT-PCR data revealed that prex is present as a single transcript but western blot analysis of Plasmodium falciparum asexual parasite extracts revealed smaller size proteins indicating post-translational cleavage of the protein. Gene knock out studies have shown that the Pfprex genome locus is recombinogenic although parasites with a disrupted Pfprex locus appear to be unable to survive in culture. The analysis of the recombinant polymerase domain confirmed the polymerase property of the protein.

In Toxoplasma gondii, the gene (Tgprex) is 7,740 bp long and interrupted by 19 introns as identified by RT-PCR. The polymerase functionality of the PREX protein was also confirmed by a study on recombinant protein from Toxoplasma gondii. The recombinant protein can be inhibited by known family A polymerase inhibitors.

Other related apicomplexan parasites including Theileria, Babesia and Eimeria also possess this prex homologous gene in their nuclear genome.

This PREX protein, apparently an amalgamation of functions derived from viral and bacterial origins, is probably important for maintenance of genomic integrity of the apicoplast. The recombinant protein and the assay system may provide the platform for screening of compounds for future drug search against the apicomplexan parasites.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences > Molecular Biosciences
Supervisor's Name: Barrett, Dr. Mike
Date of Award: 2006
Depositing User: Angi Shields
Unique ID: glathesis:2006-4347
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 03 Jun 2013 10:17
Last Modified: 03 Jun 2013 10:17

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