A conserved pathway of cell death in response to invading DNA (2016-2019)
Abstract
Recognition of foreign DNA is a key means by which both bacteria and eukaryotic cells can detect infections, as well as guard their own genome. Eukaryotic cell DNA is sequestered in the nucleus and organelles, and any DNA found in the cytosol is a danger signal. We propose that cytosolic DNA-induced cell death is a fundamental eukaryotic defensive response, but surprisingly, the known pathway is restricted to macrophages of some mammals. We have found lytic cell death is elicited within ten minutes of introduction of long genomic DNA into the cytosol of cells from insects, birds and mammals. In this project we aim to characterize molecular details of this new pathway of foreign DNA recognition and rapid cell death.