Deciphering and Simulating Models of Radiation Genotoxicity with CRISPR/Cas9 Systems

Publication date: Available online 3 February 2020Source: Mutation Research/Reviews in Mutation ResearchAuthor(s): Dusan Vukmirovic, Colin Seymour, Carmel MothersillAbstractThis short review explores the utility and applications of CRISPR/Cas9 systems in experimentally simulating genotoxic effects of Ionizing Radiation (IR) to determine the contribution of DNA targets and ‘Complex Double-Stranded Breaks (complex DSBs)’ to the response. To elucidate this objective, this review considers applications of CRISPR/Cas9 to target nuclear DNA to recognize the respective ‘nucleocentric’ response as well as mitochondrial DNA (mtDNA) - an often under-recognized target in radiobiology. This requires accurate experimental simulation of IR-like effects and parameters with the CRISPR/Cas9 systems. Therefore, the role of anti-CRISPR proteins in modulating enzyme activity to simulate dose rate - an important factor in radiobiology experiments is an important topic of this review. The applications of auxiliary domains on the Cas9 nuclease to simulate oxidative base damage and multiple stressor experiments are also topics of discussion. Ultimately, incorporation of CRISPR/Cas9 experiments into computational parameters in radiobiology models of IR damage and shortcomings to the technology is discussed as well. Altogether, the simulation of IR parameters and lack of damage to non-DNA targets in the CRISPR/Cas9 system lends this rapidly, emerging tool as an effective model of DNA induced I...

Source: Mutation Research Reviews in Mutation Research - February 4, 2020 Category: Genetics & Stem Cells Source Type: research