Topoisomerases. In one gate, out the other.
The ability of type II DNA topoisomerases to pass one DNA double helix through another can be explained by a mechanism involving two gates in the enzyme structure.
Adenosine Triphosphate↗
Biomedical subjects
G Orphanides
Publications and source records attributed to G Orphanides.
Evidence for a conformational change in the DNA gyrase-DNA complex from hydroxyl radical footprinting.
We have used the technique of hydroxyl radical footprinting to probe the complex between DNA gyrase and a 198 bp DNA fragment containing the preferred gyrase cleavage site from plasmid pBR322. We find that gyrase protects 128 bp from the hydroxyl radical with the central 13 bp (adjacent to the gyrase cleavage site) being most strongly protected. Flanking the central region are arms showing periodic protection from the reagent suggesting a helical repeat of 10.6 bp, consistent with the DNA being wrapped upon the enzyme surface. The presence of 5'-adenylyl-beta,gamma-imidodiphosphate or a quinolone drug causes alteration of the protection pattern consistent with a conformational change in the complex involving one arm of the wrapped DNA. The significance of these results for the mechanism of DNA supercoiling by gyrase is discussed.
Base Sequence↗
Emerging evidence for the interrelationship of xenobiotic exposure and circadian rhythms: a review.
The circadian clock controls many aspects of mammalian physiology and behaviour with a periodicity of approximately 24 h. These include the anticipation of, and adaptation to, daily environmental changes such as the light-dark cycle, temperature fluctuations and the availability of food. The toxicity of many drugs is dependent on the circadian phase at which they are administered, and recent work has begun to unravel the molecular basis for circadian variations in sensitivity to xenobiotic exposure. Between 2 and 10% of the transcriptome is expressed in a circadian manner, including many key genes associated with the metabolism and transport of xenobiotics. Furthermore, a number of xenobiotics may directly alter the expression of genes that control circadian rhythms. This review discusses the emerging evidence for the regulation of circadian rhythm genes having an important impact on molecular response to xenobiotics.
Animals↗