Molecular phenomena in DNA damaged by ionizing radiation

This seminar is dedicated to a combined theoretical and experimental investigation of the structure and dynamics of two common types of defects occurring in the DNA molecule, after chemical or radiation damage: base mismatches and strand breaks. Base mismatches are local deviations from the ideal Watson-Crick pairing rules. Strand breaks are lesions to the DNA backbone, defined by the cleavage of the phosphodiester bond. Both such defects could occur either naturally, from imperfections in the cell process, or environment- and artificially induced, such as in cancer radiotherapy.

Using single-molecule force spectroscopy performed by optical tweezers and accompanied by Molecular Dynamics (MD) all-atom simulations, we demonstrate that it is possible to experimentally detect a single base-pair mismatch in short DNA hairpins.
Subsequently, we designed structural models for the DNA strand-break defects, in the two key constitutive elements of the chromatin: the DNA linker and the nucleosome. Using different techniques (Essential Dynamics, steered MD, covariant mechanical stress) we characterized the early stages of the evolution of this DNA lesion in the two elements.

Ciro Cecconi - ciro.cecconi@unimore.it