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

The phosphorylation of histone variant H2AX and formation of gamma H2AX is a primary response to the DNA doublestrand breaks (DSBs). Detection of gamma H2AX 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 gamma H2AX and cell death and so gamma H2AX can serve as a surrogate marker of drug-induced cytotoxicity. Recent advances in genomic research offer an opportunity to detect gamma H2AX 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 gamma H2AX biomarker as a powerful tool in genotoxicity analyses for the monitoring and managing of cancer diseases.

Automated summary

The phosphorylation of histone variant H2AX and the formation of gamma H2AX are primary responses to DNA double-strand breaks, serving as robust and sensitive tools for diagnosing DNA damage and repair in pre-clinical drug discovery investigations. Gamma H2AX can also serve as a surrogate marker for drug-induced cytotoxicity, while recent advances in genomic research allow for its detection as a specific biomarker for quantitatively analyzing DNA damages and repair. The use of gamma H2AX as a biomarker shows promise in genotoxicity analyses and the monitoring and management of cancer diseases.