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

Keller A, Rackwitz J, Cauët E, Liévin J, Körzdörfer T, Rotaru A, Gothelf KV, Besenbacher F, Bald I - Sci Rep (2014)

Bottom Line: 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.Thus, the present results suggest the development of targeted radiosensitizers for cancer radiation therapy.

View Article: PubMed Central - PubMed

Affiliation: 1] 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.

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.

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(a) DNA strand break yields of similar sequences as shown above (Figure 2), only the central T bases have been replaced by BrU. The incorporation of BrU leads to a slight increase in σSSB, but the A containing sequence remains the most fragile one. (b) The enhancement factor is displayed, which is largest for the G containing sequences. The results indicate that the variation of σSSB due to different nucleotide sequences is stronger than the enhancement upon BrU incorporation.
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f3: (a) DNA strand break yields of similar sequences as shown above (Figure 2), only the central T bases have been replaced by BrU. The incorporation of BrU leads to a slight increase in σSSB, but the A containing sequence remains the most fragile one. (b) The enhancement factor is displayed, which is largest for the G containing sequences. The results indicate that the variation of σSSB due to different nucleotide sequences is stronger than the enhancement upon BrU incorporation.

Mentions: 5-Bromouracil (BrU) is a well-known radiosensitizer, whose incorporation into DNA by replacing T increases the SSB and DSB yields upon irradiation with electrons and photons343536. We have studied the effect of BrU incorporation on the strand break cross sections by using the sequences discussed above and replacing the three central T bases by BrU. The absolute strand break cross sections determined for 18 eV electron irradiation are shown in Fig. 3a. Again, the TT(ABrUA)3TT sequence exhibits the highest σSSB, whereas the TT(CBrUC)3TT sequence has the lowest σSSB. There is only a small difference between TT(CBrUC)3TT and TT(GBrUG)3TT, but the cross section of TT(ABrUA)3TT is about twice as high as that of TT(CBrUC)3TT. The exact values of σSSB of the different sequences are summarized in Table 1.


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

Keller A, Rackwitz J, Cauët E, Liévin J, Körzdörfer T, Rotaru A, Gothelf KV, Besenbacher F, Bald I - Sci Rep (2014)

(a) DNA strand break yields of similar sequences as shown above (Figure 2), only the central T bases have been replaced by BrU. The incorporation of BrU leads to a slight increase in σSSB, but the A containing sequence remains the most fragile one. (b) The enhancement factor is displayed, which is largest for the G containing sequences. The results indicate that the variation of σSSB due to different nucleotide sequences is stronger than the enhancement upon BrU incorporation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260214&req=5

f3: (a) DNA strand break yields of similar sequences as shown above (Figure 2), only the central T bases have been replaced by BrU. The incorporation of BrU leads to a slight increase in σSSB, but the A containing sequence remains the most fragile one. (b) The enhancement factor is displayed, which is largest for the G containing sequences. The results indicate that the variation of σSSB due to different nucleotide sequences is stronger than the enhancement upon BrU incorporation.
Mentions: 5-Bromouracil (BrU) is a well-known radiosensitizer, whose incorporation into DNA by replacing T increases the SSB and DSB yields upon irradiation with electrons and photons343536. We have studied the effect of BrU incorporation on the strand break cross sections by using the sequences discussed above and replacing the three central T bases by BrU. The absolute strand break cross sections determined for 18 eV electron irradiation are shown in Fig. 3a. Again, the TT(ABrUA)3TT sequence exhibits the highest σSSB, whereas the TT(CBrUC)3TT sequence has the lowest σSSB. There is only a small difference between TT(CBrUC)3TT and TT(GBrUG)3TT, but the cross section of TT(ABrUA)3TT is about twice as high as that of TT(CBrUC)3TT. The exact values of σSSB of the different sequences are summarized in Table 1.

Bottom Line: 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.Thus, the present results suggest the development of targeted radiosensitizers for cancer radiation therapy.

View Article: PubMed Central - PubMed

Affiliation: 1] 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.

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.

Show MeSH