The plastid DNA of the malaria parasite Plasmodium falciparum is replicated by two mechanisms.
In common with other apicomplexan parasites, Plasmodium falciparum, a causative organism of human malaria, harbours a residual plastid derived from an ancient secondary endosymbiotic acquisition of an alga. The function of the 35 kb plastid genome is unknown, but its evolutionary origin and genetic content make it a likely target for chemotherapy. Pulsed field gel electrophoresis and ionizing radiation have shown that essentially all the plastid DNA comprises covalently closed circular monomers, together with a tiny minority of linear 35 kb molecules. Using two-dimensional gels and electron microscopy, two replication mechanisms have been revealed. One, sensitive to the topoisomerase inhibitor ciprofloxacin, appears to initiate at twin D-loops located in a large inverted repeat carrying duplicated rRNA and tRNA genes, whereas the second, less drug sensitive, probably involves rolling circles that initiate outside the inverted repeat.
National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. dwillia@nimr.mrc.ac.uk
D H
DH
Williamson
P R
PR
Preiser
P W
PW
Moore
S
S
McCready
M
M
Strath
R J M
RJ
Wilson
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D004270:DNA, Circular / Q000096:biosynthesis* / Q000235:genetics / Q000648:ultrastructure; D016054:DNA, Protozoan / Q000096:biosynthesis* / Q000235:genetics / Q000648:ultrastructure; D016521:Electrophoresis, Gel, Pulsed-Field; D015180:Electrophoresis, Gel, Two-Dimensional; D008854:Microscopy, Electron; D008957:Models, Genetic; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000648:ultrastructure; D018087:Plastids / Q000187:drug effects / Q000235:genetics* / Q000648:ultrastructure; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors; D059005:Topoisomerase II Inhibitors
D000890:Anti-Infective Agents; D004270:DNA, Circular; D016054:DNA, Protozoan; D015800:Protozoan Proteins; D059005:Topoisomerase II Inhibitors; D002939:Ciprofloxacin