title: Radioresistance of GGG sequences to prompt strand break formation from direct-type radiation damage.
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.
authors.affiliation: Department of Radiation Oncology, Columbia University, New York, NY, 10027, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Black
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA. adam.miller@yale.edu.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Miller
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester, Rochester, NY, 14642, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hayes
mesh_terms: D001483:Base Sequence; D053960:DNA Breaks / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*
keywords: DNA damage; Direct effect; Gel electrophoresis; Guanine; Ionizing radiation; Radiation chemistry; Radiosensitivity