Computational Studies of the Mechanical Stability for Single-Strand Break DNA

Abstract

The stability of DNA is crucial for the existence of most living organisms. Even a single DNA break can lead to serious problems, including cell death. In this work the position specificity of single strand breaks (SSB) and the stability of short DNA fragments of various lengths and sequence repetitions (d(AT), d(ATGC), d(GC), d(TTAGG), d(TTAGGG), and d(TTTAGGG) with SSBs and d(GC) with 2-60 repetitions without SSBs) were examined, by performing a series of steered molecular dynamics simulations using the coarse-grained NARES-2P force field. Our results show that the stability of DNA with a SSB strongly depends on the position of the break, and that the minimum length of DNA required for stability is sequence dependent. d(GC) with an SSB in position x was found to be less resistant to stretching than d(GC) without SSB, where x is the number of d(GC) repetitions. DNA sequences with longer repeated fragments (such as telomeres) exhibit greater stability in the presence of breaks positioned at the beginning of the chain, which could constitute a cellular defense mechanism against DNA damage.

Theory and Practice of Coarse-Grained Molecular Dynamics of Biologically Important Systems

“…With limited restraints, NARES-2P is capable of modeling complex DNA and RNA folds [ 173 ]. NARES-2P was used to investigate telomere stability [ 174 ] and the influence of single-strand breaks on the mechanical stability of various DNA chains [ 175 ].…”