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A precise equation of equilibrium of four steps of TBP binding with the TATA box for prognosis of phenotypic manifestation of mutations

  • Molecular Biophysics
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Abstract

Among the central events of transcription initiation of TATA-containing genes in eukaryotes are the recognition and binding of the TATA box by the TATA-binding protein (TBP) to start the preinitiation complex formation on nucleosomal DNA. Using the equation of equilibrium for step-by-step TBP/TATA binding, we have analyzed 69 experimental datasets for the characteristics of biologically important features altered by TATA-box mutations. Among these features, the TBP/TATA-complex parameters, the transcription level, the activity of gene products, yeast colony growth at a dose of growth inhibitor (phenotype), and the heterogeneity of the response of a population to unspecific environmental stress have been described. Significant correlations were found between in silico prediction for TBP/TATA affinity and experimental data for in vivo and in vitro test systems based on 15 cell types of 19 species, RNA polymerases II and III, and natural, recombinant or mutant TBP. Such an invariant impact of the step-by-step TBP/TATA binding on the biological activity of complex systems, from a molecule to a population, might be due to the fact that TBP/TATA-complex formation precedes specific steps of transcription machinery assembly, which provide the multivariant jigsaw puzzle according to the expression pattern of each eukaryotic gene.

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Original Russian Text © P.M. Ponomarenko, V.V. Suslov, L.K. Savinkova, M.P. Ponomarenko, N.A. Kolchanov, 2010, published in Biofizika, 2010, Vol. 55, No. 3, pp. 400–414.

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Ponomarenko, P.M., Suslov, V.V., Savinkova, L.K. et al. A precise equation of equilibrium of four steps of TBP binding with the TATA box for prognosis of phenotypic manifestation of mutations. BIOPHYSICS 55, 358–369 (2010). https://doi.org/10.1134/S0006350910030036

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