Base-pair lifetime

Rephcation errors, even with a very efficient repair system, lead to the accumulation of mutations. A human has 10 nucleated cells each with 3 X 10 base pairs of DNA. If about 10 cell divisions occur in a lifetime and 10 mutations per base pair per cell generation escape repair, there may evenmaUy be as many as one mutation per 10 bp in the genome. Formnately, most of these will probably occur in DNA that does not encode proteins or will not affect the function of encoded proteins and so are of no consequence. In addition, spontaneous and chemically induced damage to DNA must be repaired. 

It has been shown that photoexcitation of the guanine-cytosine (G-C) base pair leads to proton transfer [231], Watson-Crick (WC) base pairs have excited state lifetimes much shorter than other non-WC base pairs indicating once again that the natural occurring WC base pairs are more photostable than other alternative configurations [115, 118, 232-235], Much work has been done in the gas phase where many different base pair isomers exist. The ultrafast relaxation of the WC base pair has also been confirmed in solution using fluorescence up-conversion measurements [117]. 

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... 

The fluorescence of 2AP is strongly quenched by nucleic acid bases [17, 18, 24-29]. Time-correlated single-photon counting studies have shown that the interactions of 2AP with different nucleic acid bases significantly decrease the 2AP fluorescence hfetime [17, 24-29]. While the fluorescence lifetime of free 2AP in aqueous solution is about 10 ns, in double-stranded DNA the 2AP hfetimes are reduced to 30-50 ps. This effect has been used extensively to study the dynamics of mismatched base pairs [19, 21, 25, 30], local changes in dynamics of DNA molecules produced by their binding to the active sites of polymerases [26, 31-33], stacking interactions at abasic... 

Let us assume that the lifetime of the delocalized state is limited by proton transfer between one of the base pairs such that as soon as one proton coordinate cross the XT/CT intersection, the delocalized state collapses to from a localized state. Assuming the usual Condon separation between the nuclear and electronic dynamics, we can write this within the non-adiabatic Marcus approximation... 

The theoretical. Sj nonradiative lifetimes by Markwick and Doltsinis [55] are in agreement with recent experimental observations [2, 79] which suggest that the canonical base pairs are extremely short-lived, the GC lifetime being of the order of 100 fs. This is also in accord with the scenario sketched by ab initio... 

Figure 10-19. Excited state population (squares) of the GC base pair in the gas phase as a function of time after vertical photoexcitation. Nonradiative lifetimes of Tj = 31 4 fs and r2 = 293 49 fs have been determined from a bi-exponential fit (solid line) a mono-exponential fit (dashed line) gives a lifetime of 89 8 fs...

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. 

The implication is that under the conditions of deep UV irradiation, which likely existed on the early earth, selective chemistry may have taken place in favor of species with the shortest excited state lifetimes. Benner and coworkers, for example, have proposed a molecular lexicon of 12 alternate bases that can produce 6 base pairs with virtually identical geometries as the guanine-cytosine (GC) triply hydrogen bonded base pair [1], Several of these alternate bases have been observed as products in simulation experiments that test the feasibility of synthesis of such compounds under primitive conditions [77, 78], This raises the... 

In this chapter we have reviewed computations that help to explain the photostability and lifetimes of the DNA nucleobases, using cytosine and the cytosine-guanine Watson-Crick base-pair as examples. 

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