Repair of DNA Lesions by a Reductive Electron Tansfer

Thomas Carell, Christoph Behrens, Nicole Rahe, and Michaela K. Cichon

Department of Chemistry, Philipps-University, Hans-Meerwein-Str., D-35043 Marburg, Germany




Electron transfer phenomena in DNA are of fundamental importance for DNA damage [1] and DNA repair[2]. The movement of a positive charge (hole) through DNA [3-6] has been shown to proceed over significant distances. Two mechanisms, namely coherent superexchange (kET~e-beta r) for small transfer distances and hole (lnkET~eta lnN), or polaron hopping for long range transfer are used to describe this phenomenon. In contrast to hole transfer, little is known about the transport of excess electrons (negative charges) through a DNA duplex. Such an excess electron transfer, however, is important in biology because DNA photolyase enzymes repair UV-induced cyclobutane pyrimidine dimer lesions (T=T) in the DNA duplex by an electron transfer from a reduced an deprotonated FADH--cofactor (Fl) to the dimer lesion.

The presentation covers recent results obtained in our group about the distance dependence of an excess electron transfer in a defined donor-DNA-acceptor system [7,8]. The prepared DNA double strands contain a reduced flavin electron donor and a thymine dimer acceptor, separated by adenine:thymine (A:T)n bridges of various lengths. The electron injection is initiated by irradiation of the DNA-double strand at 360 nm, which causes excitation of the reduced and deprotonated flavin donor (Fl). The injected electron, if captured by the dimer (T=T), triggers subsequently a cycloreversion, which is detectable by HPLC.

A plot of the observed splitting yields ln(yield per minute) against the distance Delta r(Å) between the flavin donor and the dimer gave a straight line with a small beta-value of beta = 0.1 Å-1. Such small beta-values were determined for long range hole transfer as well. Our data show that excess electron transfer proceeds similarly efficient. Plotting of the yield data according to the hopping model ln(yield per minute) against ln(N) by assuming that every T between the flavin donor and the dimer acceptor can function as a discrete charge carrier (N), gives a straight line with a reasonable eta-value of close to 2. The result indicates that the charge transfer proceed by hopping.