APE1 is a master regulator of the ATR-/ATM-mediated DNA damage response.

To maintain genomic integrity, cells have evolved several conserved DNA damage response (DDR) pathways in response to DNA damage and stress conditions. Apurinic/apyrimidinic endonuclease 1 (APE1) exhibits AP endonuclease, 3'-5' exonuclease, 3'-phosphodiesterase, and 3'-exoribonuclease activities and plays critical roles in the DNA repair and redox regulation of transcription. However, it remains unclear whether and how APE1 is involved in DDR pathways.

Immunostimulatory nucleic acid nanoparticles (NANPs) augment protective osteoblast and osteoclast type I interferon responses to Staphylococcus aureus.

Recalcitrant staphylococcal osteomyelitis may be due, in part, to the ability of Staphylococcus aureus to invade bone cells. However, osteoclasts and osteoblasts are now recognized to shape host responses to bacterial infection and we have recently described their ability to produce IFN-β following S. aureus infection and limit intracellular bacterial survival/propagation.

cGAS Mediates the Inflammatory Responses of Human Microglial Cells to Genotoxic DNA Damage.

Genomic instability is a key driving force for the development and progression of many age-related neurodegenerative diseases and central nervous system (CNS) cancers. Recently, the cytosolic DNA sensor, cyclic GMP-AMP synthase (cGAS), has been shown to detect and respond to self-DNA accumulation resulting from DNA damaging insults in peripheral cell types. cGAS has been shown to be important in the responses of microglia to DNA viruses and amyloid beta, and we have reported that it underlies the responses of human microglia to exogenous DNA.

Cytosolic DNA sensors and glial responses to endogenous DNA.

Genomic instability is a key driving force for the development and progression of many neurodegenerative diseases and central nervous system (CNS) cancers. The initiation of DNA damage responses is a critical step in maintaining genomic integrity and preventing such diseases. However, the absence of these responses or their inability to repair genomic or mitochondrial DNA damage resulting from insults, including ionizing radiation or oxidative stress, can lead to an accumulation of self-DNA in the cytoplasm.