Gamma-H2AX - a novel biomarker for DNA double-strand breaks.
When DNA damage, whether it is endogenous or exogenous, forms double stranded breaks (DSBs), it is always followed by the phosphorylation of the histone, H2AX. H2AX is a variant of the H2A protein family, which is a component of the histone octomer in nucleosomes. It is phosphorylated by kinases such as ataxia telangiectasia mutated (ATM) and ATM-Rad3-related (ATR) in the PI3K pathway. This newly phosphorylated protein, gamma-H2AX, is the first step in recruiting and localizing DNA repair proteins. DSBs can be induced by mechanisms such as ionizing radiation or cytotoxic agents and subsequently, gamma-H2AX foci quickly form. These foci represent the DSBs in a 1:1 manner and can be used as a biomarker for damage. An antibody can be raised against gamma-H2AX which can therefore be visualized by immunofluorescence through secondary antibodies. The detection and visualization of gamma-H2AX by flow cytometry allow the assessment of DNA damage, related DNA damage proteins and DNA repair. Gamma-H2AX also has other applications in the detection of genomic damage caused by cytotoxic chemical agents and environmental and physical damage, especially in the context of cancer treatment and therapy.
Kuo
Linda J
LJ
Radiobiology Laboratory, California Pacific Medical Center Research Institute, San Francisco, CA 94118, USA.
Yang
Li-Xi
LX
D000818:Animals; D015415:Biomarkers; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation
D015415:Biomarkers; D006657:Histones