Berlin 2024 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 4: Computational Biophysics I
BP 4.6: Vortrag
Montag, 18. März 2024, 16:15–16:30, H 0112
Kinetics of radiation-induced DNA double-strand breaks through coarse-grained simulations — •Manuel Micheloni1,2, Lorenzo Petrolli1,2, Gianluca Lattanzi1,2, and Raffaello Potestio1,2 — 1Physics Department, University of Trento, via Sommarive, 14 I-38123 Trento, Italy — 2INFN-TIFPA, Trento Institute for Fundamental Physics and Applications, I-38123 Trento, Italy
Double-strand breaks (DSBs), the covalent cut of the DNA backbone over both strands, are a detrimental outcome of cell irradiation. The earliest stages of the irradiation of DNA feature fast and localized processes, hardly characterizable by conventional experimental techniques, but viable for in silico assessments; mean-field descriptions have been extremely insightful at correlating irradiation regimes and macroscopic observables (i.e. cell survival), albeit neglecting structural, mechanical and kinetic implications associated with lesioned DNA molecules. In fact, in spite of their biological significance, the dynamical evolution of DSBs is still largely uncertain. Via coarse-grained molecular dynamics simulations, we have addressed the mechanical rupture of a DNA molecule by diverse DSB motifs, i.e., within a range of distances between strand breaks (DSB distance). We have shown the cooperative nature of the process, characterized by an abrupt transition driven by the disruption of the residual interactions between DNA moieties, governed by Poisson statistics. Moreover, we have accessed the timescales of the rupturing process, inferring an exponential dependence of the characteristic rupture times on the DSB distances, typically associated with an Arrhenius-like law of thermally-activated processes.
Keywords: Coarse-grained molecular dynamics simulations; Nucleic acids; oxDNA force field; DNA lesions; Radiation biophysics