Reactive Molecular Dynamics Simulation on DNA Double Strand Breaks Induced by Hydrogen Elimination

TL;DR

This study uses reactive molecular dynamics to model how hydrogen elimination induces double-strand breaks in telomeric DNA, revealing specific conditions under which DSBs occur.

Contribution

It introduces a scar model for simulating DNA damage from hydrogen elimination and identifies key conditions for double-strand break formation.

Findings

DSBs observed with more than 24 scars

Single-strand breaks occur with fewer scars

DSBs require scars on both strands and in close proximity

Abstract

We propose a scar model to reproduce how double-strand breaks occur in the telomeric DNA damaged by the effect of the $\beta$-decay of tritium to helium. In this scar model, the two hydrogens bonded to the 5$^\prime$ carbon connecting the pent saccharides and phosphate are removed. Molecular dynamics simulations using the reactive force field are carried out for 10 cases for the telomeric DNA consisting of 16 base pairs (32 nucleotides). It results in double-strand breaks (DSBs) being observed for structures with more than 24 scars. For 16 scar cases, only single-strand breaks (SSB) are observed. Moreover, in the case of $\left\{16, 0 \right\}$ and $\left\{ 0, 16 \right\},$ where only one of the strands had scars, SSB occurs only in the scarred strand. Secondly, in the $\left\{16, 8 \right\}$ and $\left\{ 8, 16 \right\}$ cases, DSBs occurs. Therefore, we conclude that the following conditions are necessary for DSBs:(i) Scars must occur on both the L and R strands. (ii) A large number of scars (24 or more) must occur in close proximity to each other.