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Sequence dependence of electron-induced DNA strand breakage revealed by DNA nanoarrays

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  • Adrian Keller, Institute of Ion Beam Physics and Materials Research, Helmholtz-Zentrum Dresden-Rossendorf
  • ,
  • Jenny Rackwitz, Institute of Chemistry - Physical Chemistry, University of Potsdam, Tyskland
  • Emilie Cauët, Université Libre de Bruxelles, Belgien
  • Jacques Liévin, Université Libre de Bruxelles, Danmark
  • Thomas Körzdörfer, Université Libre de Bruxelles, Institute of Chemistry - Physical Chemistry, University of Potsdam, Belgien
  • Alexandru Rotaru, Center of Advanced Research in Bionanoconjugates and Biopolymers, "Petru Poni" Institute of Macromolecular Chemistry, Danmark
  • Kurt Vesterager Gothelf
  • Flemming Besenbacher
  • Ilko Bald, Institute of Chemistry - Physical Chemistry, University of Potsdam, Dept. of Analytic Chemistry, BAM Federal Institute for Materials Research and Testing, Berlin, Danmark
The electronic structure of DNA is determined by its nucleotide sequence, which is for instance exploited in molecular electronics. Here we demonstrate that also the DNA strand breakage induced by low-energy electrons (18 eV) depends on the nucleotide sequence. To determine the absolute cross sections for electron induced single strand breaks in specific 13 mer oligonucleotides we used atomic force microscopy analysis of DNA origami based DNA nanoarrays. We investigated the DNA sequences 5'-TT(XYX)3TT with X = A, G, C and Y = T, BrU 5-bromouracil and found absolute strand break cross sections between 2.66 · 10(-14) cm(2) and 7.06 · 10(-14) cm(2). The highest cross section was found for 5'-TT(ATA)3TT and 5'-TT(ABrUA)3TT, respectively. BrU is a radiosensitizer, which was discussed to be used in cancer radiation therapy. The replacement of T by BrU into the investigated DNA sequences leads to a slight increase of the absolute strand break cross sections resulting in sequence-dependent enhancement factors between 1.14 and 1.66. Nevertheless, the variation of strand break cross sections due to the specific nucleotide sequence is considerably higher. Thus, the present results suggest the development of targeted radiosensitizers for cancer radiation therapy.
TidsskriftScientific Reports
StatusUdgivet - 9 dec. 2014

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