Partial purification and characterization of DNA polymerase β-like enzyme from Plasmodium falciparum

Nunthawarasilp, Prapa; Petmitr, Songsak; Chavalitshewinkoon-Petmitr, Porntip

doi:10.1016/j.molbiopara.2007.04.011

Cited by 11 publications

(9 citation statements)

References 31 publications

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“…In agreement with this study, several proteins involved in short‐patch BER was not identified in P. falciparum (e.g., polymerase β, ligase 3) (cf Table ). It has to be mentioned that although a protein with polymerase β‐like enzyme activity has been reported in P. falciparum , its role in short‐patch BER in P. falciparum has not been confirmed. As it is responsible for the synthesis of 3‐ to 5‐bp oligonucleotides, it may be involved in long‐patch repair .…”

Section: Resultsmentioning

confidence: 99%

“…It has to be mentioned that although a protein with polymerase β‐like enzyme activity has been reported in P. falciparum , its role in short‐patch BER in P. falciparum has not been confirmed. As it is responsible for the synthesis of 3‐ to 5‐bp oligonucleotides, it may be involved in long‐patch repair . Also, this ‘polymerase β‐like’ protein may have another role in an alternative end‐joining pathway in the parasite .…”

Section: Resultsmentioning

confidence: 99%

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Uracil moieties in Plasmodium falciparum genomic DNA

et al. 2018

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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 Plasmodium DNA . 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 .

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Uracil moieties in Plasmodium falciparum genomic DNA

et al. 2018

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“…The biochemistry and enzymology of nuclear Plasmodium DNA replication has been restricted to the cloning and characterization of some replication factors like PfORC1, PfMCMs (mini-chromosome-maintenance proteins), PfPCNA, PfRPA and few DNA polymerase enzymes (Ridley et al, 1991;Kilbey et al, 1993;Patterson et al, 2002;Voss et al, 2002;Mehra et al, 2005;Gupta et al, 2006;Patterson et al, 2006;Nunthawarasilp et al, 2007). Few Plasmodium homologues of cyclins and cdk-like kinases have been reported (Doerig et al, 2002;Ward et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum origin recognition complex subunit 5: functional characterization and role in DNA replication foci formation

Gupta¹,

Mehra²,

Dhar³

2008

Molecular Microbiology

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SummaryThe mechanism of DNA replication initiation and progression is poorly understood in the parasites, including human malaria parasite Plasmodium falciparum. Using bioinformatics tools and yeast complementation assay, we identified a putative homologue of Saccharomyces cerevisiae origin recognition complex subunit 5 in P. falciparum (PfORC5). PfORC5 forms distinct nuclear foci colocalized with the replication foci marker proliferating cell nuclear antigen (PfPCNA) and co-immunoprecipitates with PCNA during early-to-mid trophozoite stage replicating parasites. Interestingly, these proteins separate from each other at the non-replicating late schizont stage, citing the evidence of the presence of both PCNA and ORC components in replication foci during eukaryotic DNA replication. PfORC1, another ORC subunit, colocalizes with PfPCNA and PfORC5 at the beginning of DNA replication, but gets degraded at the late schizont stage, ensuring the regulation of DNA replication in the parasites. Further, we have identified putative PCNA-interacting protein box in PfORC1 that may explain in part the colocalization of PfORC and PfPCNA. Additionally, use of specific DNA replication inhibitor hydroxyurea affects ORC5/PCNA foci formation and parasitic growth. These results strongly favour replication factory model in the parasites and confer great potential to understand the co-ordination between ORC and PCNA during eukaryotic DNA replication in general.

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“…Till now genes for three members of the ORC family of proteins (namely PfORC1, 2 and 5) have been cloned from P. falciparum and their role in erythrocytic replication has been established (Gupta et al, 2006;Mehra et al, 2005). Besides ORCs, several other replicating proteins have also been identified and characterized in P. falciparum, namely minichromosomal maintenance proteins (MCM2-7), DNA polymerase enzymes, PCNA1 and PCNA2, PfRPA (Ridley et al, 1991;Patterson et al, 2002;Gupta et al, 2006;Nunthawarasilp et al, 2007;Voss et al, 2002) although their precise role has not been elucidated in parasite biology. Studies using radioactive nucleotides incorporation in parasite culture have shown a window (~22-36 hours post-invasion) where replication takes place during asexual blood stages (Inselburg & Banyal, 1984;Arnot & Gull, 1998).…”

Section: -Biological Processes From a Signalling Perspectivementioning

confidence: 99%

Signalling in malaria parasites – The MALSIG consortium

et al. 2009

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Summary :Depending on their developmental stage in the life cycle, malaria parasites develop within or outside host cells, and in extremely diverse contexts such as the vertebrate liver and blood circulation, or the insect midgut and hemocoel. Cellular and molecular mechanisms enabling the parasite to sense and respond to the intra-and the extra-cellular environments are therefore key elements for the proliferation and transmission of Plasmodium, and therefore are, from a public health perspective, strategic targets in the fight against this deadly disease. The MALSIG consortium, which was initiated in February 2009, was designed with the primary objective to integrate research ongoing in Europe and India on i) the properties of Plasmodium signalling molecules, and ii) developmental processes occurring at various points of the parasite life cycle. On one hand, functional studies of individual genes and their products in Plasmodium falciparum (and in the technically more manageable rodent model Plasmodium berghei) are providing information on parasite protein kinases and phosphatases, and of the molecules governing cyclic nucleotide metabolism and calcium signalling. On the other hand, cellular and molecular studies are elucidating key steps of parasite development such as merozoite invasion and egress in blood and liver parasite stages, control of DNA replication in asexual and sexual development, membrane dynamics and trafficking, production of gametocytes in the vertebrate host and further parasite development in the mosquito. This article, which synthetically reviews such signalling molecules

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Partial purification and characterization of DNA polymerase β-like enzyme from Plasmodium falciparum

Cited by 11 publications

References 31 publications

Uracil moieties in Plasmodium falciparum genomic DNA

Uracil moieties in Plasmodium falciparum genomic DNA

Plasmodium falciparum origin recognition complex subunit 5: functional characterization and role in DNA replication foci formation

Signalling in malaria parasites – The MALSIG consortium

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