Tautomerism, base pairs

Tautomerism and base pairing. Tautomerism has an interesting relationship to the formation of the pairs and triplets of hydrogen bonds in DNA or RNA. Each base exists predominately as one preferred... 

Based on your analysis, is it likely that tautomeric equilibria involving the nucleotide bases will interfere noticeably with base pairing in DNA Explain. 

Sobolewski AL, Domcke W, Hattig C (2005) Tautomeric selectivity of the excited-state lifetime of guanine/cytosine base pairs The role of electron-driven proton-transfer processes. Proc Natl Acad Sci USA 102 17903-17906... 

Recently, we reported observations of the femtosecond dynamics of tautomerization in model base pairs (7-azaindole dimers) containing two hydrogen bonds. Because of the femtosecond resolution of proton motions, we were able to examine the cooperativity of formation of the tautomer (in... 

The process of mutation by tautomerization is similar to the excited-state process described here. If a misprint induced by a tautomer takes place during replication, then an error is recorded. Because reaction path calculations of DNA base pairs show similar potential-energy characteristics to those discussed here, we anticipate being able to explore the relevance of tautomerization dynamics to mutagenesis. In this area, we are currently examining these and other systems, also in solutions. 

Femtosecond Molecular Dynamics of Tautomerization in Model Base Pairs, A. Douhal, S. K. Kim, and A. H. Zewail, Nature 378, 260 (1995). 

B. Kohler 1 would like to ask two questions to Prof. Zewail. First, in your investigation of the electron transfer reaction in a benzene- complex, the sample trajectory calculations you showed appear to suggest that the charge transfer step may induce vibrationally coherent motion in h-. Have you tested this possibility experimentally My second question concerns your intriguing results on a tautomerization reaction in a model base-pair system. In many of the barrierless chemical reactions you have studied, you have been able to show that an initial coherence created in the reactant molecules is often observable in the products. In the case of the 7-azaindole dimer system your measurements indicate that reaction proceeds quite slowly on the time scale of vibrational motions (such as the N—H stretch) that are coupled to the reaction coordinate. What role do you think coherent motion might play in reactions such as this one that have a barrier ... 

J. -L. Martin Prof. Zewail, how do you expect your work on pho-toinduced tautomerization of base pairs to apply to the real world of DNA, where such a reaction would happen on ground-state potential surface in a water environment ... 

Nucleoside analogues do not always behave as expected. 5-Bromouracil (6.a) effectively forms base pairs with guanine nucleotides. This surprising observation has been explained by invoking a different tautomer of 6.a. Draw a different tautomer of 6.a and show how it can effectively base pair to a guanine nucleotide. (Tautomerization theory Topal, M. D., Fresco, J. R. Base Pairing and... 

Fig. 3. The effect of rare tautomeric forms on the change in the base-pairing scheme and its perpetuation through DNA replication.

Mistakes in base incorporation can be made this is largely a result of the transient existence of tautomeric forms of the bases (Chap. 7). If at the instant of insertion of a new nucleotide by DNA polymerase the base in the template shifts to its rare tautomeric form, which has altered base-pairing specificity, an incorrect nucleotide may be added to the chain e.g., one containing guanine instead of adenine opposite the enol form of thymine. 

This enzyme has a proofreading role. At a low random frequency, incorrect bases (in the form of nucleotides) are inserted into the growing DNA chain. This results from the existence of rare tautomeric forms of the four bases, which, if occurring transiently in the template at the moment of insertion of an incoming nucleotide, will cause a mistake in base pairing. When such a template nucleotide shifts back to its preponderant form, a base pair mismatch results. The 3 —>5 exonuclease recognizes the mismatch and catalyzes the hydrolytic removal of the nucleotide from the end of the chain before elongation resumes. 

Another approach of great importance for studies of excited state dynamics is sub-picosecond time resolved spectroscopy. A number of authors have reported femtosecond pump-probe measurements of excited state lifetimes in A, C, T, and G [13-16] and base pair mimics [17]. Schultz et al. have reported time resolved photoelectron spectroscopy and electron-ion coincidence of base pair mimics [18]. these studies can also be compared with similar measurements in solution [19-24], While time resolved measurements provide direct lifetime data, they do have the limitation that the inherent bandwidth reduces the spectral resolution, required for selecting specific electronic states and for selecting single isomers, such as cluster structure and tautomeric form. 

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