Synthesis of DNA during the asexual cycle of Plasmodium falciparum in culture

Inselburg, Joseph; Banyal, H. S.

doi:10.1016/0166-6851(84)90020-3

Cited by 97 publications

(51 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Replication in intraerythrocytic parasites begins between 28 and 31 hpi and continues until the end of schizogony (8). Accordingly, P. falciparum replication factors like DNA pol ␣ (60), DNA pol ␦ (61), topoisomerases I (62) and II (63), and proliferating cell nuclear antigen (61) are expressed in trophozoites and schizonts.…”

Section: Fig 4 Limited Trypsin Digestionmentioning

confidence: 99%

“…Several genes involved in eukaryotic chromosomal DNA replication and their encoded proteins have been identified in this parasite, including DNA polymerases ␣ (DNA pol ␣) 1 (1,2) and ␦ (DNA pol ␦) (3,4), proliferating cell nuclear antigen (5), and topoisomerases I (6) and II (7). It has been shown that expression of these genes follows a stagespecific pattern coinciding with the beginning of chromosomal replication which starts 28 -31 h after merozoite invasion and continues through most of schizogony (8).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Plasmodium falciparum Possesses a Cell Cycle-regulated Short Type Replication Protein A Large Subunit Encoded by an Unusual Transcript

Voss¹,

Mini²,

Jenoe³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

DNA replication in Plasmodium parasites takes place at multiple distinct points during their complex life cycle in the mosquito and vertebrate hosts. Although several parasite proteins involved in DNA replication have been described, the various mechanisms engaged in DNA metabolism of this major pathogen remain largely unexplored. As a step toward understanding this complex network, we describe the identification of Plasmodium falciparum replication protein A large subunit (pfRPA1) through affinity purification and mass spectral analysis of a purified 55-kDa factor. Gel retardation experiments revealed that pfRPA is the major singlestranded DNA binding activity in parasite protein extracts. The activity was expressed in a cell cycle-dependent manner with peak activities in late trophozoites and schizonts, thus correlating with the beginning of chromosomal DNA replication. Accordingly, the pfrpa1 message was detected in parasites 20 -24 h post-invasion which is in agreement with the expression of other P. falciparum DNA replication genes. Our results show that pfRPA1 is encoded by an unusual 6.5-kb transcript containing a single open reading frame of which only the C-terminal 42% of the deduced protein sequence shows homologies to other reported RPA1s. Like the orthologues of other protozoan parasites, pfRPA1 lacks the N-terminal protein interaction domain and is thus remarkably smaller than the RPA1s of higher eukaryotes.Plasmodium falciparum causes one of the most life-threatening parasitic diseases in humans being responsible for up to 2 million deaths per year. Malaria pathogenesis is associated with the intracellular erythrocytic stage of the life cycle of the parasite involving repeated rounds of invasion, growth, and schizogony. Parasites that eventually differentiate into gametocytes are taken up by the female anopheline vector where zygote formation and sporogony take place. Sporozoites injected into a human host by the bite of an infective mosquito invade hepatocytes and, after schizogony, release thousands of merozoites capable of invading red blood cells. During each replication event, the timing, rate, and extent of genome multiplication have to be controlled appropriately and coordinated at each developmental stage. Most of the studies on DNA replication in P. falciparum have been conducted during the erythrocytic stages. Several genes involved in eukaryotic chromosomal DNA replication and their encoded proteins have been identified in this parasite, including DNA polymerases ␣ (DNA pol ␣) 1 (1, 2) and ␦ (DNA pol ␦) (3, 4), proliferating cell nuclear antigen (5), and topoisomerases I (6) and II (7). It has been shown that expression of these genes follows a stagespecific pattern coinciding with the beginning of chromosomal replication which starts 28 -31 h after merozoite invasion and continues through most of schizogony (8).Due to their complex life cycle and constant immunological pressure exerted by their hosts, the processes of DNA metabolism in Plasmodium parasites must be both very efficient a...

show abstract

Section: Fig 4 Limited Trypsin Digestionmentioning

confidence: 99%

mentioning

confidence: 99%

Plasmodium falciparum Possesses a Cell Cycle-regulated Short Type Replication Protein A Large Subunit Encoded by an Unusual Transcript

Voss¹,

Mini²,

Jenoe³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…It has been known for many years that bulk DNA synthesis starts in blood stage culture in late trophozoites (47,57,91,99), not long before the onset of the nuclear divisions that mark the start of schizogony. It is now known that both mtDNA and nuclear DNA start replicating together (87,99).…”

Section: Replicationmentioning

confidence: 99%

Extrachromosomal DNA in the Apicomplexa

Wilson¹,

Gardner²,

Rangachari³

et al. 1993

Toxoplasmosis

View full text Add to dashboard Cite

“…Each of the synchronized schizogonic stages was subjected to in vitro uniform drug pressure for 12 hr with the differential outcome with regard to parasite survival and multiplication. Intraerythrocytic merozoites in the schizont and the early rings are the least susceptible to toxic effects of cisplatin, perhaps in these stages, no active DNA synthesis takes place (26) and the parasite plasma membrane is the most intact, thus retarding free entry of the compound into the parasite milieu. Cisplatin is known to prevent the multiplication of cancer cells by random inter-and intralinking of DNA strands of these dividing cells (27).…”

Section: Discussionmentioning

confidence: 99%

Cure With Cisplatin (Ii) of Murine Malaria Infection and in Vitro Inhibition of a Chloroquine-Resistant Plasmodium Falciparum Isolate

Nair

Bhasin

1994

JJMSB

View full text Add to dashboard Cite

SUMMARY:Antiplasmodium properties of cisplatin [cis-platinum (II) diammine dichloride], a neoplastic drug, have been assessed in in vivo and in vitro model systems of malarial parasite. A well-tolerated dose of 6 mg/kg body weight of the compound cured the mice infected with Plasmodium berghei and the amount of cisplatin required for in vitro inhibition (IC50) of a chloroquineresistant Plasmodium falciparum isolate was smaller than either chloroquine or quinine. The minimum inhibitory concentration (MIC) needed to prevent the in vitro multiplication of asexual blood parasites was 30 ng/ml. Late ring and trophozoite stages of the erythrocytic cycle were the most susceptible, whereas schizont and early ring stages were the least sensitive to the toxic effect of cisplatin. Multiple smaller doses were more effective in curing malaria in mice than a single large dose. In a few of the mice treated with a single intraperitoneal large dose of 6 mg/kg body weight, there was a delay in appearance of parasitemia but most of them recovered completely but slowly. This compound exerts its toxicity mainly by randomly damaging and cross-linking DNA strands as shown by Southern hybridization with a synthetic oligonucleotide probe, which is a repeat sequence in the falciparum genome. The report clearly demonstrates the antimalarial potentials of this compound and suggests a closer evaluation of this and other related compounds, specially in combination with antimalarial drugs to probe their synergistic properties.241

show abstract

Synthesis of DNA during the asexual cycle of Plasmodium falciparum in culture

Cited by 97 publications

References 9 publications

Plasmodium falciparum Possesses a Cell Cycle-regulated Short Type Replication Protein A Large Subunit Encoded by an Unusual Transcript

Plasmodium falciparum Possesses a Cell Cycle-regulated Short Type Replication Protein A Large Subunit Encoded by an Unusual Transcript

Extrachromosomal DNA in the Apicomplexa

Cure With Cisplatin (Ii) of Murine Malaria Infection and in Vitro Inhibition of a Chloroquine-Resistant Plasmodium Falciparum Isolate

Contact Info

Product

Resources

About