Axial distortion as a sensor of supercoil changes: a molecular model for the homeostatic regulation of DNA gyrase.
Negative supercoiling stimulates transcription of many genes. In contrast, transcription of the genes coding for DNA gyrase is subject to a novel mechanism of autoregulation, wherein relaxation of the template DNA stimulates their transcription. Since DNA gyrase is the sole supercoiling activity in the eubacterial cell, relaxation-stimulated transcription (RST) could reflect an autoregulatory mechanism to maintain supercoil levels within the cell. Extensive deletion and mutational analyses of Escherichia coli gyrA promoter have shown that the -10 region is essential for RST; however, a molecular model has proved to be elusive. We find a strong bend centre immediately downstream of the -10 region in the gyrA promoter. On the basis of analysis of various mutants in the -10 region, we propose a model where axial distortion acts as a sensor of topological changes in DNA. Our model is consistent with earlier data with E. coli gyrA anmd gyrB promoters. We also extrapolate the model to explain the phenomenon of RST of gyr promoters in other organisms and contrast it with promoters induced by supercoiling.
Unniraman
S
S
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India.
Nagaraja
V
V
D000465:Algorithms; D001483:Base Sequence; D016384:Consensus Sequence; D027081:DNA Gyrase / Q000235:genetics*; D004252:DNA Mutational Analysis; D004278:DNA, Superhelical / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D013698:Templates, Genetic; D015533:Transcriptional Activation
D004278:DNA, Superhelical; D027081:DNA Gyrase