@article {380,
	title = {Three mitochondrial DNA polymerases are essential for kinetoplast DNA replication and survival of bloodstream form Trypanosoma brucei.},
	journal = {Eukaryot Cell},
	volume = {10},
	year = {2011},
	month = {2011 Jun},
	pages = {734-43},
	abstract = {Trypanosoma brucei, the causative agent of human African trypanosomiasis, has a complex life cycle that includes multiple life cycle stages and metabolic changes as the parasite switches between insect vector and mammalian host. The parasite{\textquoteright}s single mitochondrion contains a unique catenated mitochondrial DNA network called kinetoplast DNA (kDNA) that is composed of minicircles and maxicircles. Long-standing uncertainty about the requirement of kDNA in bloodstream form (BF) T. brucei has recently eroded, with reports of posttranscriptional editing and subsequent translation of kDNA-encoded transcripts as essential processes for BF parasites. These studies suggest that kDNA and its faithful replication are indispensable for this life cycle stage. Here we demonstrate that three kDNA replication proteins (mitochondrial DNA polymerases IB, IC, and ID) are required for BF parasite viability. Silencing of each polymerase was lethal, resulting in kDNA loss, persistence of prereplication DNA monomers, and collapse of the mitochondrial membrane potential. These data demonstrate that kDNA replication is indeed crucial for BF T. brucei. The contributions of mitochondrial DNA polymerases IB, IC, and ID to BF parasite viability suggest that these and other kDNA replication proteins warrant further investigation as a new class of targets for the development of antitrypanosomal drugs.},
	keywords = {Cell Survival, Cells, Cultured, DNA Replication, DNA, Kinetoplast, DNA-Directed DNA Polymerase, Humans, Membrane Potential, Mitochondrial, Mitochondria, Parasitemia, RNA Interference, Trypanosoma brucei brucei, Trypanosomiasis, African},
	issn = {1535-9786},
	doi = {10.1128/EC.05008-11},
	author = {Bruhn, David F and Sammartino, Mark P and Klingbeil, Michele M}
}
@article {382,
	title = {Mitochondrial DNA polymerase POLIB is essential for minicircle DNA replication in African trypanosomes.},
	journal = {Mol Microbiol},
	volume = {75},
	year = {2010},
	month = {2010 Mar},
	pages = {1414-25},
	abstract = {The unique mitochondrial DNA of trypanosomes is a catenated network of minicircles and maxicircles called kinetoplast DNA (kDNA). The network is essential for survival, and requires an elaborate topoisomerase-mediated release and reattachment mechanism for minicircle theta structure replication. At least seven DNA polymerases (pols) are involved in kDNA transactions, including three essential proteins related to bacterial DNA pol I (POLIB, POLIC and POLID). How Trypanosoma brucei utilizes multiple DNA pols to complete the topologically complex task of kDNA replication is unknown. To fill this gap in knowledge we investigated the cellular role of POLIB using RNA interference (RNAi). POLIB silencing resulted in growth inhibition and progressive loss of kDNA networks. Additionally, unreplicated covalently closed precursors become the most abundant minicircle replication intermediate as minicircle copy number declines. Leading and lagging strand minicircle progeny similarly declined during POLIB silencing, indicating POLIB had no apparent strand preference. Interestingly, POLIB RNAi led to the accumulation of a novel population of free minicircles that is composed mainly of covalently closed minicircle dimers. Based on these data, we propose that POLIB performs an essential role at the core of the minicircle replication machinery.},
	keywords = {DNA Polymerase beta, DNA Replication, DNA, Kinetoplast, Gene Silencing, Protozoan Proteins, Trypanosoma brucei brucei},
	issn = {1365-2958},
	doi = {10.1111/j.1365-2958.2010.07061.x},
	author = {Bruhn, David F and Mozeleski, Brian and Falkin, Laurie and Klingbeil, Michele M}
}
