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Radioresistance of GGG sequences to prompt strand break formation from direct-type radiation damage

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Abstract

As humans, we are constantly exposed to ionizing radiation from natural, man-made and cosmic sources which can damage DNA, leading to deleterious effects including cancer incidence. In this work, we introduce a method to monitor strand breaks resulting from damage due to the direct effect of ionizing radiation and provide evidence for sequence-dependent effects leading to strand breaks. To analyze only DNA strand breaks caused by radiation damage due to the direct effect of ionizing radiation, we combined an established technique to generate dehydrated DNA samples with a technique to analyze single-strand breaks on short oligonucleotide sequences via denaturing gel electrophoresis. We find that direct damage primarily results in a reduced number of strand breaks in guanine triplet regions (GGG) when compared to isolated guanine (G) bases with identical flanking base context. In addition, we observe strand break behavior possibly indicative of protection of guanine bases when flanked by pyrimidines and sensitization of guanine to strand break when flanked by adenine (A) bases in both isolated G and GGG cases. These observations provide insight into the strand break behavior in GGG regions damaged via the direct effect of ionizing radiation. In addition, this could be indicative of DNA sequences that are naturally more susceptible to strand break due to the direct effect of ionizing radiation.

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Acknowledgments

The investigation was supported by PHS Grant R01 CA32546, awarded by National Cancer Institute, DHHS. Miller was currently supported by NIH Grant R01 GM057814. Hayes was currently supported by NIH Grant R01 GM052426.

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    Authors and Affiliations

    1. Department of Radiation Oncology, Columbia University, New York, NY, 10027, USA

      Paul J. Black

    2. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA

      Adam S. Miller

    3. Department of Biochemistry and Biophysics, University of Rochester, Rochester, NY, 14642, USA

      Jeffrey J. Hayes

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    1. Paul J. Black
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    Correspondence to Adam S. Miller.

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    Paul J. Black and Adam S. Miller contributed equally to this work.

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    Black, P.J., Miller, A.S. & Hayes, J.J. Radioresistance of GGG sequences to prompt strand break formation from direct-type radiation damage. Radiat Environ Biophys 55, 411–422 (2016). https://doi.org/10.1007/s00411-016-0660-7

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