Investigation of Excess‐Electron Transfer in DNA Double‐Duplex Systems Allows Estimation of Absolute Excess‐Electron Transfer and CPD Cleavage Rates

Abstract

To investigate the parameters and rates that determine excess-electron transfer processes in DNA duplexes, we developed a DNA double-duplex system containing a reduced and deprotonated flavin donor at the junction of two duplexes with either the same or different electron acceptors in the individual duplex substructures. This model system allows us to bring the two electron acceptors in the duplex substructures into direct competition for injected electrons and this enables us to decipher how the kind of acceptor influences the transfer data. Measurements with the electron acceptors 8-bromo-dA (BrdA), 8-bromo-dG (BrdG), 5-bromo-dU (BrdU), and a cyclobutane pyrimidine dimer, which is a UV-induced DNA lesion, allowed us to obtain directly the maximum overall reaction rates of these acceptors and especially of the T=T dimer with the injected electrons in the duplex. In line with previous observations, we detected that the overall dimer cleavage rate is about one order of magnitude slower than the debromination of BrdU. Furthermore, we present a more detailed explanation of why sequence dependence cannot be observed when a T=T dimer is used as the acceptor and we estimate the absolute excess-electron hopping rates.

Charge transfer dynamics in DNA revealed by time-resolved spectroscopy

“…More recently, they suggested that the hopping rate through the (A : T) 4 pair is faster than 1.8 × 10 7 s –1 and slower than 1.4 × 10 8 s –1 based on the comparison of the EET rate through DNA with the debromination rate of BrU or cleavage rate of the T dimer. 41 …”

Charge transfer in DNA

“…From electron spin resonance (ESR) studies on γ-ray radiated DNA, Sevilla et al estimated the β value of single-step EET at 77 K to be 0.8-1.2 Å -1 [27]. In addition, several research groups reported that the excess electron migrates in DNA by means of the multistep hopping mechanism [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. Thus, the actual rate constant is necessary for further detailed understanding of EET in DNA.…”

DNA Radiosensitization: The Search for Repair Refractive Lesions Including Double Strand Breaks and Interstrand Crosslinks

“…Indeed, recently a more effective electron transfer has been reported for mismatched duplexes than for fully complementary DNA (Ito et al, 2009). Using a two electron acceptor DNA model system with incorporated BrdA, BrdG, BrdU and TT-dimer Fazio et al (Fazio et al, 2011) were able to estimate the absolute electron-hoping rates in DNA and have shown that the electron transfer is more efficient in 5' → 3' direction. As mentioned, in unsubstituted DNA pyrimidine rather than purine bases have been considered as trapping sites for excess electrons.…”