Document Type : Review Article
Department of Microbiology, Wilson College, Mumbai 400007, Maharashtra, India
Double Strand Breaks (DSBs) are the most deleterious DNA lesions among the first signs of cancer in eukaryotic cells. Occurring on exposure to one or more endogenous and/or exogenous factors and leading to fatal consequences like chromosome aberrations and genomic instability. Therefore, programmed and coordinated cellular processes function intra-cellular to stabilize the genomic information and repair damages. These processes are primarily a part of DNA replication and cell-cycle progression. However, various signaling factors also activate specialized DNA Damage Response (DDR) pathways for repairing DSBs. Lately, the phosphorylated histone variant H2AX (γH2AX) has been identified as a biomarker for DNA damage. Studies have shown a correlation between the concentration of cellular γH2AX and the extent of DNA damage. Hence, the quantification of DNA lesions can be done using simple spectroscopic and radiological techniques or immunofluorescent staining. For this reason, γH2AX has especially gained value as a biomarker in translational cancer research. Moreover, this approach may act as a boon in clinical trial studies for understanding the different phases of cancer and studying the pharmacodynamics of prospective drugs. Recently, γH2AX based studies have indicated the indispensable fate of DNA damages occurring during normal neurological development and in disorders like obesity. The current review focuses on the role of γH2AX in DDR pathways, and ways in which the correlation of γH2AX and DNA damage can be applied in monitoring the clinical response of DNA targeted therapies.