In Silico Non-Homologous End Joining Following Ion Induced DNA Double Strand Breaks Predicts That Repair Fidelity Depends on Break Density.

ABSTRACT: This work uses Monte Carlo simulations to investigate the dependence of residual and misrepaired double strand breaks (DSBs) at 24 hours on the initial damage pattern created during ion therapy. We present results from a nanometric DNA damage simulation coupled to a mechanistic model of Non-Homologous End Joining, capable of predicting the position, complexity, and repair of DSBs. The initial damage pattern is scored by calculating the average number of DSBs within 70 nm from every DSB. We show that this local DSB density, referred to as the cluster density, can linearly predict misrepair regardless of ion species. The models predict that the fraction of residual DSBs is constant, with 7.3% of DSBs left unrepaired following 24 hours of repair. Through simulation over a range of doses and l

SUBMITTER: Henthorn NT 

PROVIDER: S-EPMC5805743 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature