Project 458755

When our cells are exposed to DNA-damaging agents, such as UV light from the sun or the chemotherapeutic drugs commonly used for cancer treatment, pieces of DNA can break off from our chromosomes. Those broken pieces of DNA remain inside the cell, but outside the DNA-containing nucleus, where DNA is not supposed to be. DNA outside the nucleus is usually a sign that a cell has been infected by a DNA virus. Viral protein receptors can mistake your own damaged DNA fragments for a piece of a DNA virus, and alert your immune system. Through these viral receptors, the DNA damage-immune system axis lets your body eliminate damaged cells before they have the chance to develop into cancer. However, not all of those DNA fragments, here called MICRONUCLEI, are recognized by viral receptors. The features of micronuclear DNA that attract or dissuade viral receptors are not known. My preliminary work has shown that the likelihood of a specific viral receptor, named cGAS, binding micronuclear DNA depends on the particular kind of DNA damage to which the cell was initially exposed. This means that certain types of DNA damage activate your immune system easily, while other kinds of damage are indolent, for reasons currently unclear. My research will uncover the DNA and protein components of micronuclei that are generated by different kinds of DNA damage, and the specific micronuclear characteristics that attract the viral receptor cGAS. This work will uncover key features of the DNA damage-immune system axis, which could be leveraged into more targeted therapeutic regimens for DNA damage-induced cancers.