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

Keller A1, Rackwitz J2, Cauët E3, Liévin J3, Körzdörfer T2, Rotaru A4, Gothelf KV5, Besenbacher F5, Bald I6.

Sci Rep. 2014 Dec 9;4:7391. doi: 10.1038/srep07391.

Abstract

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.

Author information

11]Interdisciplinary Nanoscience Center (iNANO) and Danish National Research Foundation: Centre for DNA Nanotechnology (CDNA), Aarhus University, 8000 Aarhus C, Denmark [2] Institute of Ion Beam Physics and Materials Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.

2Institute of Chemistry – Physical Chemistry, University of Potsdam, Potsdam, Germany.

3Université Libre de Bruxelles, 1050 Brussels, Belgium.

4Center of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, Romania.

5Interdisciplinary Nanoscience Center (iNANO) and Danish National Research Foundation: Centre for DNA Nanotechnology (CDNA), Aarhus University, 8000 Aarhus C, Denmark.

61] Interdisciplinary Nanoscience Center (iNANO) and Danish National Research Foundation: Centre for DNA Nanotechnology (CDNA), Aarhus University, 8000 Aarhus C, Denmark [2] Institute of Chemistry – Physical Chemistry, University of Potsdam, Potsdam, Germany [3] BAM Federal Institute of Materials Research and Testing, Berlin, Germany.

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