The H circles of Leishmania tarentolae are a unique amplifiable system of oligomeric DNAs associated with drug resistance.

作者: T C White , F Fase-Fowler , H van Luenen , J Calafat , P Borst

DOI: 10.1016/S0021-9258(18)37486-6

关键词: Extrachromosomal DNAHomologous chromosomeBiologyGel electrophoresisGene duplicationGeneticsPlasmidBacteriaMolecular biologyStrain (chemistry)Dihydrofolate reductase

摘要: We have induced drug resistance against methotrexate, an inhibitor of dihydrofolate reductase, and CB3717, thymidylate synthetase in a strain Leishmania tarentolae. The drug-resistant strains contain extrachromosomal DNA circles 68 kilobases with 30-kilobase inverted duplication flanked by 4- 5 kilobase unique segments. show that these are highly homologous to the drug-induced H L. tropica (1). All three tarentolae analyzed chromosomal copy region without duplication, but two as well, predominantly present circle dimers one tetramers other. After induction methotrexate resistance, monomeric circles, presumably derived from oligomers, become major type circle. Our results indicate represents genomic can be copied at very low frequency yield precise, unusual mechanism under natural conditions wild-type cells. Although superficially analogous episomes bacteria, system is precedent nature.

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