Recent advances in γH2AX biomarker-based genotoxicity assays: A marker of DNA damage and repair

Abstract

The phosphorylation of histone variant H2AX and formation of γH2AX is a primary response to the DNA double-strand breaks (DSBs). Detection of γH2AX is a robust and sensitive tool for diagnosis of DNA damage and repair in pre-clinical drug discovery investigations. In addition, the replication stress also leads to the formation of γH2AX and cell death and so γH2AX can serve as a surrogate marker of drug-induced cytotoxicity. Recent advances in genomic research offer an opportunity to detect γH2AX as a specific biomarker for quantitative analysis of DNA damages and repair using high content screening technology and quantitative imaging analysis. The proposed approaches identify a wide range of genetic disorders and are applied in combination with other assays in drug discovery and also for the evaluation of the efficacy of various developmental drugs. In the current review, we provide recent insights into the potential of γH2AX biomarker as a powerful tool in genotoxicity analyses for the monitoring and managing of cancer diseases.

Keywords: DNA damage; Genetic imaging; Genotoxicity; H2A histone family; γH2AX.