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By Robert Balthazaar

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J Biol Chem 2001; 276(18):14614–14622. 74. Pardo L, Pastor N, Weinstein H. Selective binding of the TATA box-binding protein to the TATA box-containing promoter: analysis of structural and energetic factors. Biophys J 1998; 75(5):2411–2421. 75. de Souza ON, Ornstein RL. Inherent DNA curvature and flexibility correlate with TATA box functionality. Biopolymers 1998; 46(6):403–415. 76. Qian X, Strahs D, Schlick T. Dynamic simulations of 13 TATA variants refine kinetic hypotheses of sequence/activity relationships.

Parikh and coworkers suggest that damaged sites along the DNA may allow greater compression than undamaged sites and that the combination of backbone compression and insertion of the Leu 272 side chain into the minor groove facilitates flipping of the uracil through the major groove. Base flipping requires the loss of favorable stacking interactions between adjacent bases and the breakage of hydrogen bonds with the complementary base, which can amount to approximately 3–7 kcal/mol depending on the particular dinucleotide step (38,39).

While the AU base pair is not directly mutagenic, some transcription factors have significantly reduced binding affinity for AU compared to AT base pairs (28). Thus, although the eukaryotic replicative polymerases are high fidelity enzymes, with misincorporation occurring at a rate of approximately 10À7 per base pair per generation (29), this non-negligible finite probability leads to undesired biological consequences. In humans, spontaneous deamination of cytosine occurs at a rate of approximately 100–500 events per cell per day (30).

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Active Dreaming: The Key to Power by Robert Balthazaar


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