The effect of bacterial DNA gyrase inhibitors on DNA synthesis in mammalian mitochondria.

Article Details

Citation

Castora FJ, Vissering FF, Simpson MV

The effect of bacterial DNA gyrase inhibitors on DNA synthesis in mammalian mitochondria.

Biochim Biophys Acta. 1983 Sep 9;740(4):417-27.

PubMed ID
6309236 [ View in PubMed
]
Abstract

Using isolated rat liver mitochondria, which have previously been shown to carry out true replicative DNA synthesis, we have obtained results which are in accord with the presence and functioning of a DNA gyrase in this organelle. The effects of the Escherichia coli DNA gyrase inhibitors, novobiocin, coumermycin, nalidixic acid and oxolinic acid, upon mtDNA replication suggest the involvement of the putative mitochondrial enzyme in various aspects of this process. First, the preferential inhibition of [3H]dATP incorporation into highly supercoiled DNA together with the appearance of labeled, relaxed DNA are consistent with the involvement of a gyrase in the process of generating negative supercoils in mature mtDNA. Second, the overall depression of incorporation of labeled dATP into mtDNA, including the reduction of radioactivity incorporated into replicative intermediates, suggests a 'swivelase' role for the putative gyrase, and this hypothesis is further supported by results obtained on sucrose gradient centrifugation of heat-denatured, D-loop mtDNA. Here, the synthesis of the completed clean circles is inhibited while 9 S initiator strand synthesis is not, suggesting that chain elongation is blocked by the gyrase inhibitors.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
EnoxacinDNA gyrase subunit AProteinHaemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Yes
Inhibitor
Details