Sequence-dependent variations of DNA structure modulate radiation-induced strand breakage

• Published in: International journal of radiation biology Vol. 72; no. 2; pp. 147 - 155
• Main Author: SY, C. SAVOYE, M. BEGUSOVA, V. MICHALIK, M. CHARLIER and M. SPOTHEIM-MAURIZOT, D.
• Format: Journal Article
• Language: English
• Published: London Informa UK Ltd 01-08-1997; Taylor & Francis
• Subjects: Base Sequence; Biological and medical sciences; Biological effects of radiation; DNA - chemistry; DNA - radiation effects; DNA Damage; Fundamental and applied biological sciences. Psychology; Ionizing radiations; Models, Molecular; Molecular Sequence Data; Monte Carlo Method; Nucleic Acid Conformation; Plasmids - genetics; Space life sciences; Tissues, organs and organisms biophysics; Monte Carlo method; Radiosensitivity; Nucleotide sequence; Stochastic simulation; Biophysics; In vitro; Modeling; Chromosome break; Ionizing irradiation; Radiobiology; DNA; Nucleotide; Neutron beam; Biological effect; Molecular biology
• ISSN: 0955-3002; 1362-3095
• DOI: 10.1080/095530097143365

Using a 80 base pair DNA fragment, the sequencedependence was compared for: (i) the probability of fast neutrons induced strand breakage, (ii) the accessibility of the H4- and H5-atoms to OH attack, (iii) the width of the minor groove, and (iv) the probability of OH reactions with H4- or H5- atoms. The probability of strand breakage was measured using sequencing gel electrophoresis. The accessibility and the probability of reaction were calculated for the energy-minimized modelled DNA fragment. A Monte-Carlo simulation was used for calculating the probabilities of H-atom abstraction by OH. It was observed that reduced breakage occurs in sequences exhibiting low accessibility of H4 and H5 2 and low probability of H-atom abstraction by OH, due to a narrow, minor groove. This shows that the breakage probability at a given nucleotide site is not determined by the chemical nature of the nucleotide (A, T, G or C), but mainly by the local sequence-modulated intrinsic structure. Fitting the experimental results with the calculated probabilities of reaction suggests that a C4-centered radical evolves towards a strand break three times more efficiently than the C5 one, and that half of the breaks occur via the 4-path and half via the 5-path.