Reactive molecular dynamics simulation on DNA double-strand breaks induced by hydrogen elimination

Abstract We propose a scar model to simulate double-strand breaks (DSBs) in telomeric DNA induced by the β -decay of tritium into helium. The two hydrogens bonded to the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msup> <mml:mrow> <mml:mn>5</mml:mn> </mml:mrow> <mml:mrow> <mml:mo accent="true">′</mml:mo> </mml:mrow> </mml:msup> </mml:math> carbon connecting the pentasaccharides and phosphate are removed in this scar model. Molecular dynamics simulations using a reactive force field were conducted across ten cases involving telomeric DNA composed of 16 base pairs (32 nucleotides). DSBs are observed in structures with more than 24 scars, whereas only single-strand breaks (SSBs) occur in the case with 16 scars. Moreover, in the case of {16,0} and {0,16}, where only one of the strands had scars, SSB occurs only in the scarred strand. Second, in the {16,8} and {8, 16} cases, DSBs occur. Thus, we conclude that the following conditions are necessary for DSBs: (i) scars must be present on both the left (L) and right (R) strands and (ii) a substantial number of scars (24 or more) must be in close proximity.