The cellular response to DSBs is extensive and includes recognition of the DNA lesion, signal transduction responses including modulation of the cell cycle, and, finally, repair of the DSB. The goal of the Davis lab is to uncover the mechanisms that modulate the cellular response to DSBs, with a focus on how the DNA-dependent protein kinase (DNA-PK) regulates these processes.
DNA-PK plays an essential role in the repair of DNA double-stranded breaks (DSBs) mediated by the non-homologous end-joining (NHEJ) pathway. DNA-PK is a holoenzyme consisting of a DNA-binding (Ku70/Ku80) and catalytic (DNA-PKcs) subunit. DNA-PKcs is a serine/threonine protein kinase that is recruited to DSBs via Ku70/80 and is activated once the kinase is bound to the DSB ends. Our research aims to uncover the role of DNA-PK in the recognition of DNA lesions, propagating signal transduction pathways, modulating various DNA repair pathways, and influencing DSB repair pathway choice. We use a combination of biochemistry, cell biology, microscopy, proteomics, and novel mouse models to understand how DNA-PK and post-translational modifications of DNA-PK regulate these processes.