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In vitro examining the existing prognoses how TBP binds to tata with SNP associated with human diseases

Health 2011年第9期3卷 577-583页

作者： Irina A. Drachkova Petr M. Ponomarenko Tatyana V. Arshinova Мikhail P. Ponomarenko Valentin V. Suslov Ludmila K. Savinkova Nikolay А. Kolchanov 不详

We in vitro examined the existing prognoses of the dissociation constant, KD, between ТАТА- binding Protein (TBP) and ТАТА box with single nucleotide polymorphism (SNP) associated with human diseases. Five SNPs of the genes for cytochrome P450 2A6 (associated with lung cancer), β-globin (associated with β-thalassemia), mannose binding lectin (associated with variable immunodeficiency), superoxide dismutase 1 (associated with amyotrophic lateral sclerosis) and triosephosphate isomerase (associated with anemia) fell within the range of –ln(KD;M/KD;WT) between –1.5 and –1 (here KD;WT and KD;M denote the normal ТАТА box and with SNP). The mea-surements using EMSA demonstrated that: 1) all the predictions stating that the affinity between ТВР and ТАТА boxes with SNPs would be reduced were correct;2) the departures of three predictions from the measurements fell within the confidence interval;3) all the predictions consistently underestimated actual mutational damage caused to ТАТА boxes with SNPs (a < 0.05;binomial law) and two of these predictions did so significantly (a < 0.05, Student’s t-test). This consistent underestimation seems to be associated with the damage to the context that modulates ТВP/ТАТА affinity, for example, the contact between the nucleosomal histone H3-Н4 dimer and the core promoter immediately near ТАТА boxes.

关键词： Disease Polymorphism ТАТА Box tata-binding Protein Affinity In Vitro In Silico

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