DNA Containing Cyclobutane Pyrimidine Dimers Is Released from UVB-Irradiated Keratinocytes in a Caspase-Dependent...

Solar radiation induces the formation of cyclobutane pyrimidine dimers (CPDs) and other UV photoproducts in the genomic DNA of epidermal keratinocytes. Although CPDs have been detected in urine from UV- and sun-exposed individuals, the pathway by which they arrive there and the mechanisms by which UV-induced DNA damage in the skin has systemic effects throughout the body are not clear. Consistent with previous reports that DNA associates with small extracellular vesicles that are released from a variety of cell types, we observed that a small fraction of CPDs formed in genomic DNA after UVB exposure can later be detected in the culture medium. These extracellular CPDs are found within large fragments of histone-associated DNA and are released in a time- and UVB dose‒dependent manner. Moreover, studies with both cultured cells and human skin explants revealed that CPD release into the extracellular environment is blocked by caspase inhibition, which indicates a role for apoptotic signaling in CPD release from UVB-irradiated keratinocytes. Finally, we show that this released CPD-containing DNA can be taken up by other keratinocytes. These results therefore provide possible mechanisms for the export of damaged DNA from UVB-irradiated cells and for systemic effects of UVB exposure throughout the body.