Trypanosoma brucei causes human African trypanosomiasis (HAT). The pyrrolopyrimidine AEE788 (a hit for anti-HAT drug discovery) associates with three trypanosome protein kinases. Herein we delineate the effects of AEE788 on T. brucei using chemical biology strategies. AEE788 treatment inhibits DNA replication in the kinetoplast (mitochondrial nucleoid) and nucleus. In addition, AEE788 blocks du...

Maxicircle DNA has been isolated from the kinetoplast DNA of Leishmania tarentolae culture forms by bouyant separation in CsCl in the presence of the A + T-binding dye Hoechst 33258, after liberation from the kinetoplast DNA network by cleavage with the single-hit restriction endonuclease EcoRI. The purified linearized maxicircle DNA has a density in CsCl of 1.681 g/cm3 (79% A + T) and a molecu...

African trypanosomes have a remarkable mitochondrial DNA termed kDNA (kinetoplast DNA) that contains several thousands of topologically interlocked DNA rings. Because of its highly unusual structure, kDNA has a complex replication mechanism. Our approach to understanding this mechanism is to identify the proteins involved and to characterize their function. So far approx. 30 candidate proteins ...

Kinetoplast DNA (kDNA), the trypanosomatid mitochondrial DNA, is a network containing several thousand interlocked minicircles. During kDNA synthesis, minicircles dissociate from the network, and after replication their progeny reattach to the network periphery. Using electron microscopy autoradiography, we found that newly synthesized 3H-labeled minicircles, after short labeling periods, are c...

Kinetoplast DNA of Trypanosoma brucei is composed of a network of about 10,000 interlocked minicircle DNA molecules (1.0 kilobase) that are catenated with about 50 maxicircle DNA molecules (23 kilobases). Several different DNA . DNA hybridization techniques using individual minicircle DNA sequences cloned in Escherichia coli have indicated that each minicircle molecule contains about one-fourth...