Aag-initiated base excision repair promotes ischemia reperfusion injury in liver, brain, and kidney

Ischemia reperfusion (I/R)-induced tissue injury and inflammation encompasses a wide range of human disease, including stroke, hepatic and renal failure, and myocardial infarction. Generation of highly reactive oxygen and nitrogen species during I/R results in DNA damage that is subject to numerous DNA repair processes. Base excision repair (BER) initiated by various DNA glycosylases is critical for the repair of reactive oxygen and nitrogen species (RONS)-induced DNA damage. Our data describe a new paradigm wherein the Aag BER DNA glycosylase enzyme promotes, rather than prevents, tissue injury and inflammation in liver, brain, and kidney following I/R. This finding reveals a detrimental facet of DNA repair during inflammation and presents a novel target for controlling I/R-induced injury.