DNA condensation by cysteine containing tetra-arginine ligands as a model for ionizing radiation damage to chromatin

Abstract

We examined DNA binding and condensation by AcCR4NH2 and CR4NH2 ligands. By this approach, we can model physical DNA damage by ionizing radiation. The binding constant was 1 × 106 L mol−1 at low ionic strength (ca. 10 mmol L−1 sodium ions) and the resulting condensate size was ca. 1 μm. Given the similar base pair concentrations of ca. 250 mmol L−1 in condensed DNA and chromatin, DNA damage yields by ionizing irradiation in condensates with related oligoarginine ligands are comparable to those in eukaryotic nuclei. Therefore, with the benefit of these results, we can envisage an experimental system suitable for modeling DNA damage by ionizing radiation because it reproduces well the essential conditions in cell nuclei that affect this damage, particularly the high concentrations of DNA and protein in chromatin and the resulting highly efficient radical scavenging environment.