DNA double-strand breaks (DSBs) represent one of the most dangerous forms of DNA damage. DSBs arise following exposure to ionizing radiation or radio-mimetic chemicals, but are also generated as a byproduct of normal cellular metabolism. In addition to these accidental breaks, DSBs can be introduced in a programmed manner as part of physiological processes, such as immunoglobulin (Ig) class switching in mature B lymphocytes. Efficient and accurate repair of both accidental and programmed breaks is crucial to ensure cell survival and genome stability since inefficiently or aberrantly repaired DSBs may lead to cell death, cancer-prone genome rearrangements, and inability to carry out DNA recombination processes that are crucial for the establishment of a proper Immune response. Our lab is interested in understanding the molecular mechanisms that ensure appropriate repair of DSBs, and how deregulation of these processes leads to cancer and immunodeficiencies.
Di Virgilio Lab 