Cell-free DNA: a possible stress signaling molecule

Author(s): Vasilina Sergeeva

Cell-free DNA (cfDNA) is the DNA that circulates in blood, extracellular matrix or culture medium of cells. The main source of cfDNA are dying cells. Concentration of cfDNA as well as its modifications and length can serve as markers in various diseases because these properties alter under damaging conditions or in pathology. CfDNA can become oxidized due to oxidative stress, for example, as a response to ionizing radiation. Radiation causes an increase in reactive oxygen species (ROS) and apoptosis of cells, this contributes to the pool of oxidized cfDNA. It was shown that cfDNA can penetrate into the cytoplasm of cells. CfDNA collected from the medium of irradiated cells affects control nonirradiated cells, causing elevated ROS production due to activation of NOX4, oxidative modifications of nuclear DNA, rapidly repaired DNA breaks, short-term arrest of the cell cycle, activation of DNA repair systems and of antioxidant response, inhibition of apoptosis and, thus, radioadaptive response. This is mediated through decrease in NG2, HUVEL1, TP53, BBC3, NOXA, P53AIP1, BAX, BAK, MMP, ENDOG and increase in anti-apoptotic BCL2. CfDNA from nonirradiated cells has no such effect, thus, cfDNA is a signalling molecule that causes bystander effect and adaptive response.